N-substituted benzene sulfonamides

ABSTRACT

The invention provides N-substituted benzenesulfonamides for use in treating or preventing cognitive disorders, such as Alzheimer&#39;s Disease.  
                 
 
Compounds of particular interest are defined by Formula (I), wherein R 1 , R 2 , R 3 , R 4 , and R 3′ , are as described in the specification. The invention also encompasses pharmaceutical compositions comprising compounds of Formula (I) as well as methods of treating cognitive disorders, including Alzheimer&#39;s disease using compounds of Formula (I).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. Provisional Application Ser.No. 60/552,555, filed Mar. 11, 2004, which is incorporated herein byreference in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to N-substituted benzene sulfonamides. Morespecifically, it relates to such compounds that inhibit β-amyloidpeptide release and/or its synthesis and, therefore, are useful in theprevention of cognitive disorders in patients susceptible to cognitivedisorders and/or in the treatment of patients with cognitive disordersin order to inhibit further deterioration in their condition.

2. State of the Art

Alzheimer's Disease (AD) is a degenerative brain disorder characterizedclinically by progressive loss of memory, cognition, reasoning, judgmentand emotional stability that gradually leads to profound mentaldeterioration and ultimately death. AD is a very common cause ofprogressive mental failure (dementia) in aged humans and is believed torepresent the fourth most common medical cause of death in the UnitedStates. AD has been observed in races and ethnic groups worldwide andpresents a major present and future public health problem. The diseaseis currently estimated to affect about two to three million individualsin the United States alone. AD is at present incurable. No treatmentthat effectively prevents AD or reverses its symptoms and course iscurrently known.

The brains of individuals with AD exhibit characteristic lesions termedsenile (or amyloid) plaques, amyloid angiopathy (amyloid deposits inblood vessels) and neurofibrillary tangles. Large numbers of theselesions, particularly amyloid plaques and neurofibrillary tangles, aregenerally found in several areas of the human brain important for memoryand cognitive function in patients with AD. Smaller numbers of theselesions in a more restrictive anatomical distribution are also found inthe brains of most aged humans who do not have clinical AD. Amyloidplaques and amyloid angiopathy also characterize the brains ofindividuals with Trisomy 21 (Down's Syndrome) and Hereditary CerebralHemorrhage with Amyloidosis of the Dutch Type (HCHWA-D). At present, adefinitive diagnosis of AD usually requires observing the aforementionedlesions in the brain tissue of patients who have died with the diseaseor, rarely, in small biopsied samples of brain tissue taken during aninvasive neurosurgical procedure.

The principal chemical constituent of the amyloid plaques and vascularamyloid deposits (amyloid angiopathy) characteristic of AD and the otherdisorders mentioned above is an approximately 4.2 kilodalton (kD)protein of about 39-43 amino acids designated the β-amyloid peptide(βAP) or sometimes Aβ, AβP or β/A4. β-Amyloid peptide was first purifiedand a partial amino acid sequence was provided by Glenner et al.,Biochem. Biophys. Res. Commun., 120:885-890 (1984) The isolationprocedure and the sequence data for the first 28 amino acids aredescribed in U.S. Pat. No. 4,666,829.

Molecular biological and protein chemical analyses have shown that theβ-amyloid peptide is a small fragment of a much larger precursor proteintermed the amyloid precursor protein (APP), that is normally produced bycells in many tissues of various animals, including humans. Knowledge ofthe structure of the gene encoding APP has demonstrated that β-amyloidpeptide arises as a peptide fragment that is cleaved from APP byprotease enzyme(s). Sequential processing of the precursor protein bythe enzymes referred to generically as beta- and gamma-secretases, giverise to the β-amyloid peptide fragment. Both enzymes have now beenmolecularly cloned, and characterized to differing levels.

Several lines of evidence indicate that progressive cerebral depositionof β-amyloid peptide plays a seminal role in the pathogenesis of AD andcan precede cognitive symptoms by years or decades. See, for example,Selkoe, Neuron, 6:487-498 (1991). The most important line of evidence isthe discovery that missense DNA mutations at amino acid 717 of the770-amino acid isoform of APP can be found in affected members but notunaffected members of several families with a genetically determined(familial) form of AD (Goate et al., Nature, 349:704-706 (1990);Chartier Harlan et al., Nature, 353:844-846 (1989); and Murrell et al.,Science, 254:97-99 (1991.) Another such mutation, known as the Swedishvariant, is comprised of a double mutation changinglysine⁵⁹⁵-methionine⁵⁹⁶ to asparagine⁵⁹⁵-leucine⁵⁹⁶ (with reference tothe 695 isoform was found in a Swedish family) was reported in 1992(Mullan et al., Nature Genet., 1:345-347 (1992). Genetic linkageanalyses have demonstrated that these mutations, as well as certainother mutations in the APP gene, are the specific molecular cause of ADin the affected members of such families. In addition, a mutation atamino acid 693 of the 770-amino acid isoform of APP has been identifiedas the cause of the β-amyloid peptide deposition disease, HCHWA-D, and achange from alanine to glycine at amino acid 692 appears to cause aphenotype that resembles AD is some patients but HCHWA-D in others. Thediscovery of these and other mutations in APP in genetically based casesof AD prove that alteration of APP metabolism, and subsequent depositionof its β-amyloid peptide fragment, can cause AD.

Despite the progress which has been made in understanding the underlyingmechanisms of AD and other β-amyloid peptide related diseases, thereremains a need to develop methods and compositions for treatment of thedisease(s). Ideally, the treatment methods would advantageously be basedon drugs which are capable of inhibiting β-amyloid peptide releaseand/or its synthesis in vivo.

One approach toward inhibiting amyloid peptide synthesis in vivo is byinhibiting gamma secretase, the enzyme responsible for thecarboxy-terminal cleavage resulting in production of β-amyloid peptidefragments of 40 or 42 residues in length. The immediate substrates forgamma secretase are β-cleaved, as well as α-cleaved carboxy-terminalfragments (CTF) of APP. The gamma-secretase cleavage site on β- and(α-CTF fragments occurs in the predicted transmembrane domain of APP.Inhibitors of gamma-secretase have been demonstrated to effect amyloidpathology in transgenic mouse models (Dovey, H. F., V. John, J. P.Anderson, L. Z. Chen, P. de Saint Andrieu, L. Y. Fang, S. B. Freedman,B. Folmer, E. Goldbach, E. J. Holsztynska et al. (2001). “Functionalgamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.”J Neurochem 76(1): 173-81.)

Gamma secretase is recognized to be a multi-subunit complex comprised ofthe presenilins (PS1 or PS2), Nicastrin, Aph-1, and Pen 2 (De Strooper,B. (2003). “Aph-1, Pen-2, and Nicastrin with Presenilin generate anactive gamma-Secretase complex.” Neuron 38(1): 9-12; Edbauer, D., E.Winkler, J. T. Regula, B. Pesold, H. Steiner and C. Haass (2003).“Reconstitution of gamma-secretase activity.” Nat Cell Biol 5(5): 486-8;Kimberly, W. T., M. J. LaVoie, B. L. Ostaszewski, W. Ye, M. S. Wolfe andD. J. Selkoe (2003). “Gamma-secretase is a membrane protein complexcomprised of presenilin, nicastrin, Aph-1, and Pen-2.” Proc Natl AcadSci U S A 100(11): 6382-7). Much evidence indicates that PS comprisesthe catalytic moiety of the complex, while the other identified subunitsare necessary for proper maturation and sub-cellular localization of theactive enzyme complex (reviewed in De Strooper, B. (2003). “Aph-1,Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretasecomplex.” Neuron 38(1): 9-12.) Consistent with this hypothesis: PSknock-out mice exhibit significant reductions in β-amyloid production(De Strooper, B., P. Saftig, K. Craessaerts, H. Vanderstichele, G.Guhde, W. Annaert, K. Von Figura and F. Van Leuven (1998). “Deficiencyof presenilin-1 inhibits the normal cleavage of amyloid precursorprotein.” Nature 391(6665): 387-90; Haass, C. and D. J. Selkoe (1998).“Alzheimer's disease. A technical KO of amyloid-beta peptide.” Nature391(6665): 339-40; Herreman, A., L. Serneels, W. Annaert, D. Collen, L.Schoonjans and B. De Strooper (2000). “Total inactivation ofgamma-secretase activity in presenilin-deficient embryonic stem cells.”Nat Cell Biol 2(7): 461-2); point mutations of putative active siteaspartate residues in PS trans-membrane domains inhibit β-amyloidproduction in cells in a dominant negative fashion (Wolfe, M. S., W.Xia, B. L. Ostaszewski, T. S. Diehl, W. T. Kimberly and D. J. Selkoe(1999). “Two transmembrane aspartates in presenilin-1 required forpresenilin endoproteolysis and gamma-secretase activity.” Nature398(6727): 513-7; Kimberly, W. T., W. Xia, T. Rahmati, M. S. Wolfe andD. J. Selkoe (2000). “The transmembrane aspartates in presenilin 1 and 2are obligatory for gamma-secretase activity and amyloid beta-proteingeneration.” J Biol Chem 275(5): 3173-8); active site directedsubstrate-based transition state isosteres designed to inhibit gammasecretase directly conjugate to PS (Esler, W. P., W. T. Kimberly, B. L.Ostaszewski, T. S. Diehl, C. L. Moore, J. Y. Tsai, T. Rahmati, W. Xia,D. J. Selkoe and M. S. Wolfe (2000). “Transition-state analogueinhibitors of gamma-secretase bind directly to presenilin-1.” Nat CellBiol 2(7): 428-34; Li, Y. M., M. Xu, M. T. Lai, Q. Huang, J. L. Castro,J. DiMuzio-Mower, T. Harrison, C. Lellis, A. Nadin, J. G. Neduvelil etal. (2000). “Photoactivated gamma-secretase inhibitors directed to theactive site covalently label presenilin 1.” Nature 405(6787): 689-94);finally, allosteric gamma secretase inhibitors have likewise beendemonstrated to bind directly to PS (Seiffert, D., J. D. Bradley, C. M.Rominger, D. H. Rominger, F. Yang, J. E. Meredith, Jr., Q. Wang, A. H.Roach, L. A. Thompson, S. M. Spitz et al. (2000). “Presenilin-1 and -2are molecular targets for gamma-secretase inhibitors.” J Biol Chem275(44): 34086-91.) Current evidence indicates that in addition to APPprocessing leading to β-amyloid synthesis, gamma-secretase also mediatesthe intra-membrane cleavage of other type I transmembrane proteins(reviewed in Fortini, M. E. (2002). “Gamma-secretase-mediatedproteolysis in cell-surface-receptor signaling.” Nat Rev Mol Cell Biol3(9): 673-84, see also Struhl, G. and A. Adachi (2000). “Requirementsfor presenilin-dependent cleavage of notch and other transmembraneproteins.” Mol Cell 6(3): 625-36.) Noteworthy among the known substratesof gamma-secretase is mammalian Notch 1. The Notch 1 protein isimportant for cell fate determination during development, and tissuehomeostasis in the adult. Upon ligand engagement via the Notchecto-domain, Notch undergoes sequential extra-cellular andintra-membrane processing analogous to APP. The intra-membraneprocessing of Notch mediated by gamma secretase leads to release of theNotch intracellular domain (NICD). The NICD fragment mediates Notchsignaling via translocation to the nucleus, where it regulatesexpression of genes mediating cellular differentiation in many tissuesduring development, as well as in the adult.

Disruption of Notch signaling via genetic knock-out (KO) results inembryonic lethal phenotype in mice (Swiatek, P. J., C. E. Lindsell, F.F. del Amo, G. Weinmaster and T. Gridley (1994). “Notchl is essentialfor postimplantation development in mice.” Genes Dev 8(6): 707-19;Conlon, R. A., A. G. Reaume and J. Rossant (1995). “Notch1 is requiredfor the coordinate segmentation of somites.” Development 121(5):1533-45.) The Notch KO phenotype is very similar to the phenotypeobserved PS1 KO mice, and precisely reproduced by PS1/PS2 double KO mice(De Strooper et al. (1998). “Deficiency of presenilin-1 inhibits thenormal cleavage of amyloid precursor protein.” Nature 391(6665): 387-90;Donoviel, D. B., A. K. Hadjantonakis, M. Ikeda, H. Zheng, P. S. Hyslopand A. Bernstein (1999). “Mice lacking both presenilin genes exhibitearly embryonic patterning defects.” Genes Dev 13(21): 2801-10;Herreman, A., L. Serneels, W. Annaert, D. Collen, L. Schoonjans and B.De Strooper (2000). “Total inactivation of gamma-secretase activity inpresenilin-deficient embryonic stem cells.” Nat Cell Biol 2(7): 461-2.)This convergence of phenotypes observed in knock-out mice of either thesubstrate (Notch) or the enzyme (PS) suggests that inhibitors of gammasecretase that also inhibit Notch function may be limited as therapeuticagents owing to the importance of Notch function in adult tissues(Fortini, M. E. (2002). “Gamma-secretase-mediated proteolysis incell-surface-receptor signaling.” Nat Rev Mol Cell Biol 3(9): 673-84.)As APP knock-out mice develop normally and without an overt phenotypeZheng, H., M. Jiang, M. E. Trumbauer, R. Hopkins, D. J. Sirinathsinghji,K. A. Stevens, M. W. Conner, H. H. Slunt, S. S. Sisodia, H. Y. Chen etal. (1996). “Mice deficient for the amyloid precursor protein gene.” AnnNY Acad Sci 777: 421-6; Zheng, H., M. Jiang, M. E. Trumbauer, D. J.Sirinathsinghji, R. Hopkins, D. W. Smith, R. P. Heavens, G. R. Dawson,S. Boyce, M. W. Conner et al. (1995). “beta-Amyloid precursorprotein-deficient mice show reactive gliosis and decreased locomotoractivity.” Cell 81(4): 525-31, the cumulative evidence, therefore,suggests that preferred gamma secretase inhibitors would haveselectivity for inhibiting gamma secretase processing of APP over gammasecretase processing of Notch.

SUMMARY OF THE INVENTION

In a broad aspect, the invention provides compounds of Formula I:

and pharmaceutically acceptable salts thereof, wherein

-   -   R₁ is C₂-C₆ alkynyl, C₂-C₆ alkenyl, or C₁-C₈ alkyl wherein each        is optionally substituted with 1, 2, or 3 groups that are        independently C₁-C₆ alkoxy, OH, halogen, CN, C₁-C₆ thioalkoxy,        phenyl, naphthyl, C₃-C₈ cycloalkyl, NH₂, NH(C₁-C₆)alkyl,        N(C₁-C₆)alkyl(C₁-C₆ alkyl), —C(O)NH₂, —C(O)NH(C₁-C₆)alkyl,        —C(O)N(C₁-C₆)alkyl(C₁-C₆)alkyl, —C(O)phenyl, or C₁-C₆        alkoxycarbonyl,        -   wherein each of the cyclic groups is optionally substituted            with 1, 2, 3, or 4 groups that are independently halogen,            C₁-C₄ alkyl, C₁-C₄ alkoxy, NH₂, NH(C₁-C₆)alkyl,            N(C₁-C₆)alkyl(C₁-C₆ alkyl), —SO₂—(C₁-C₆)alkyl, or OH; or    -   R₁ is C₃-C₈ cycloalkyl optionally substituted with 1 or 2 groups        that are independently C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, or OH;        or    -   R₁ is heterocycloalkyl or heterocycloalkyl(C₁-C₄)alkyl wherein        the heterocycloalkyl group is piperidinyl, pyrrolidinyl,        tetrahydrofuranyl, pyrazolyl, or morpholinyl, wherein the        heterocycloalkyl groups are optionally substituted with 1 or 2        groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl,        phenyl(C₁-C₄)alkyl, OH, halogen, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl,        or C₁-C₄ alkoxycarbonyl; or    -   R₁ is heteroaryl(C₁-C₄)alkyl, wherein the heteroaryl group is        pyridyl, pyrimidyl, furanyl, or thienyl and the heteroaryl group        is optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄        alkyl, C₁-C₄ alkoxy or OH;    -   R₂ is C₁-C₈ alkyl, C₁-C₆ hydroxyalkyl, or C₂-C₈ alkenyl, each of        which is optionally substituted with 1, 2, or 3 groups that are        independently phenyl, 2H-chromenyl,        1,2,3,4-tetrahydronaphthalenyl, indolyl,        3,4-dihydronaphthalenyl, phenyl, naphthyl, C₃-C₈ cycloalkyl,        benzofuranyl, indolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl,        pyridyl, pyrimidyl, C₁-C₄ alkyl, halogen, pyrazolyl, imidazolyl,        oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, NO₂, thiadiazolyl,        furanyl, triazolyl, or CN,        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl (C₁-C₆) alkyl,            C₁-C₄ alkoxy optionally substituted with pyridyl, thiazolyl,            or methyl thiazol-5-yl, NO₂, C₁-C₄ alkyl, —S(O)_(x)—R₂₅,            —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein            -   x is 0, 1, or 2;            -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl;    -   R₃ is H, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkyl, or        CN,    -   R₄ is H, halogen, C₁-C₆ alkyl optionally substituted with        —CO₂—(C₁-C₆ alkyl), C₁-C₆ alkoxy, C₁-C₆ haloalkyl, C₁-C₆        haloalkoxy, CN, aryloxy, isocyanato, —SO₂—(C₁-C₆ alkyl), —NHR′,        —NR′R″, C₁-C₆ alkanoyl, pyridyl, or phenyl; or    -   R₃ and R₄ and the carbons to which they are attached form a        heterocycloalkyl ring which is optionally substituted with 1, 2,        or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,        halogen, or C₁-C₄ alkanoyl wherein the alkanoyl group is        optionally substituted with up to 3 halogen atoms;    -   R_(3′) is H, —SO₂—NR′R″, halogen, or    -   R₄ and R_(3′) and the carbons to which they are attached form a        phenyl ring; or    -   R₄ and R_(3′) and the carbons to which they are attached form a        1-oxa-2,3-diazacyclopentyl ring;        -   R′ is H, C₁-C₆ alkyl, phenyl(C₁-C₄)alkyl, C₁-C₆ alkanoyl,            phenyl(C₁-C₆)alkanoyl, pyridyl(C₁-C₄)alkyl,            pyrimidyl(C₁-C₄)alkyl, pyridazyl(C₁-C₄)alkyl,            pyrazinyl(C₁-C₄)alkyl, thienyl(C₁-C₄)alkyl,            oxazolyl(C₁-C₄)alkyl, thiazolyl(C₁-C₄)alkyl,            furanyl(C₁-C₄)alkyl, —SO₂-alkyl, —SO₂-phenyl, —SO₂-pyridyl,            —SO₂-pyrimidyl, —SO₂-pyridazyl, —SO₂-pyrazinyl,            —SO₂-thienyl, —SO₂-oxazolyl, —SO₂-thiazolyl, —SO₂-furanyl,            pyridyl (C₁-C₆) alkanoyl, pyrimidyl(C₁-C₆)alkanoyl,            pyridazyl(C₁-C₆)alkanoyl, pyrazinyl(C₁-C₆)alkanoyl,            thienyl(C₁-C₆)alkanoyl, oxazolyl(C₁-C₆)alkanoyl,            thiazolyl(C₁-C₆)alkanoyl, or furanyl(C₁-C₆)alkanoyl, wherein            the alkyl portion of the alkyl and alkanoyl groups are            optionally substituted with halogen or C₁-C₆ alkoxy, wherein            the aryl, and heteroaryl groups are optionally substituted            with alkyl, alkoxy, halogen, haloalkyl, haloalkoxy,        -   R″ is H, or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

The compounds of Formula I inhibit β-amyloid peptide release and/or itssynthesis and, therefore, are useful in the prevention of Alzheimer'sDisease (AD) in patients susceptible to AD and/or in the treatment ofpatients with AD in order to inhibit further deterioration in theircondition. The invention also, encompasses pharmaceutical compositionscontaining the compounds of Formula I, and methods employing suchcompounds or compositions in the treatment of cognitive diseases,including Alzheimer's disease.

The invention also provides a method of treating a patient who has, orin preventing a patient from getting, a disease or condition selectedfrom the group consisting of Alzheimer's disease, for helping prevent ordelay the onset of Alzheimer's disease, for treating patients with mildcognitive impairment (MCI) and preventing or delaying the onset ofAlzheimer's disease in those who would progress from MCI to AD, fortreating Down's syndrome, for treating humans who have HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treatingcerebral amyloid angiopathy and preventing its potential consequences,i.e. single and recurrent lobar hemorrhages, for treating otherdegenerative dementias, including dementias of mixed vascular anddegenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, age related maculardegeneration or diffuse Lewy body type of Alzheimer's disease and who isin need of such treatment which comprises administration of atherapeutically effective amount of a compound of formula (I).

In another aspect, the invention provides methods of preparing thecompounds of interest, as well as intermediates useful in preparing thecompounds of interest.

DETAILED DESCRIPTION OF THE INVENTION

In embodiment 2, the invention provides compounds of formula I wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1, 2, or        3 groups that are independently C₁-C₆ alkoxy, OH, halogen, CN,        C₁-C₆ thioalkoxy, phenyl, naphthyl, C₃-C₈ cycloalkyl, NH₂,        NH(C₁-C₆)alkyl, N(C₁-C₆)alkyl(C₁-C₆ alkyl), —C(O)NH₂,        —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆)alkyl,        —C(O)phenyl, or C₁-C₆ alkoxycarbonyl,        -   wherein each of the cyclic groups is optionally substituted            with 1, 2, 3, or 4 groups that are independently halogen,            C₁-C₄ alkyl, C₁-C₄ alkoxy, NH₂, NH(C₁-C₆) alkyl, N(C₁-C₆)            alkyl (C₁-C₆ alkyl) , —SO₂—(C₁-C₆)alkyl, or OH.

In embodiment 3, the invention provides compounds according toembodiment 2, wherein

-   -   R₃ is H, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkyl,        CN;    -   R₄ is H, halogen, C₁-C₆ alkyl optionally substituted with        —CO₂—(C₁-C₆ alkyl), C₁-C₆ alkoxy, C₁-C₄ haloalkyl, C₁-C₆        haloalkoxy, CN, aryloxy, isocyanato, —SO₂—(C₁-C₆ alkyl), —NHR′,        —NR′R″, C₁-C₆ alkanoyl, oxazolyl, pyrazolyl, thiazolyl, pyridyl,        furanyl or thienyl, phenyl; and    -   R_(3′) is H, or halogen.

Embodiment 3A. Compounds according to embodiment 3, wherein at least oneof R₃, R₄, and R_(3′) is hydrogen. In another aspect, two of R₃, R₄, andR_(3′) are hydrogen. In still another aspect, R₄ is halogen, methyl orCF₃. In yet still another aspect, R₃ and R_(3′) are hydrogen while R₄ ishalogen (preferably F or Cl, still more preferably Cl), methyl or CF₃.In yet another embodiment R₄ is Cl. In another embodiment R₄ is methyl.In still another embodiment R₄ is CF₃.

In embodiment 4, the invention provides compounds according toembodiment 3, wherein

-   -   R₂ is C₁-C₈ alkyl, or C₂-C₈ alkenyl, each of which is optionally        substituted with 1, 2, or 3 groups that are independently,        phenyl 2H-chromenyl, 1,2,3,4-tetrahydronaphthalenyl, indolyl,        3,4-dihydronaphthalenyl, phenyl, naphthyl, C₃-C₈ cycloalkyl,        benzofuranyl, indolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl,        pyridyl, pyrimidyl, C₁-C₄ alkyl, halogen, —CO₂—(C₁-C₆ alkyl),        pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl,        thiazolyl, thiadiazolyl, triazolyl, or CN,        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl (C₁-C₆) alkyl,            C₁-C₄ alkoxy optionally substituted with pyridyl, thiazolyl,            or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄            alkyl)-S(O)_(x)—R₂₅, or OH; wherein            -   x is 0, 1, or 2;            -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl.

Embodiment 4A. Compounds according to embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1, 2, or        3 groups that are independently C₁-C₄ alkoxy, OH, halogen, CN,        C₁-C₄ thioalkoxy, naphthyl, C₃-C₈ cycloalkyl, NH₂,        NH(C₁-C₆)alkyl, N(C₁-C₆)alkyl(C₁-C₆ alkyl), —C(O)NH₂,        —C(O)NH(C₁-C₆)alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆)alkyl,        —C(O)phenyl, or C₁-C₆ alkoxycarbonyl,        -   wherein each of the cyclic groups is optionally substituted            with 1, 2, or 3 groups that are independently halogen, C₁-C₄            alkyl, C₁-C₄ alkoxy, NH₂, NH(C₁-C₆)alkyl,            N(C₁-C₆)alkyl(C₁-C₆ alkyl), —SO₂—(C₁-C₆)alkyl, or OH.

Embodiment 4B. Compounds according to Embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1, 2, or        3 groups that are independently C₁-C₄ alkoxy, OH, halogen, CN,        C₁-C₄ thioalkoxy, NH₂, NH(C₁-C₆)alkyl, N(C₁-C₆)alkyl(C₁-C₆        alkyl), —C(O)NH₂, —C(O)NH(C₁-C₆)alkyl,        —C(O)N(C₁-C₆)alkyl(C₁-C₆)alkyl, —C(O)phenyl, or C₁-C₄        alkoxycarbonyl.

Embodiment 4C. Compounds according to Embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1, or 2        groups that are independently C₁-C₄ alkoxy, OH, halogen, CN,        C₁-C₄ thioalkoxy, NH₂, NH(C₁-C₄)alkyl, N(C₁-C₄)alkyl(C₁-C₄        alkyl), —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl, or C₁-C₄ alkoxycarbonyl.

Embodiment 4D. Compounds according to Embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1 or 2        groups that are independently C₁-C₄ alkoxy, OH, halogen, CN,        C₁-C₄ thioalkoxy, NH₂, NH(C₁-C₄)alkyl, or N(C₁-C₄)alkyl(C₁-C₄        alkyl).

Embodiment 4E. Compounds according to Embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1, or 2        groups that are independently C₁-C₄ alkoxy, OH, halogen, CN, or        C₁-C₄ thioalkoxy.

Embodiment 4F. Compounds according to Embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1, or 2        groups that are independently NH₂, NH(C₁-C₄)alkyl, or        N(C₁-C₄)alkyl(C₁-C₄ alkyl)

Embodiment 4G. Compounds according to Embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with 1, or 2        groups that are independently —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl, or C₁-C₄ alkoxycarbonyl.

Embodiment 4H. Compounds according to Embodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl substituted with C₃-C₈ cycloalkyl which is        optionally substituted with 1, or 2 groups that are        independently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, NH₂,        NH(C₁-C₆)alkyl, N(C₁-C₆)alkyl(C₁-C₆ alkyl), or OH.

In embodiment 5, the invention provides compounds according toembodiment 4, wherein

-   -   R₁ is C₁-C₈ alkyl which is optionally substituted with OH.

In embodiment 6, the invention provides compounds according toembodiment 5, wherein

-   -   R₃ is H, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, CF₃, CN;    -   R₄ is H, halogen, C₁-C₆ alkoxy, C₁-C₆ alkyl, CF₃, OCF₃, CN,        phenyloxy, —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₄ alkanoyl,        pyridyl, furanyl or thienyl, phenyl, or C₁-C₆ alkyl optionally        substituted with —CO₂—(C₁-C₆ alkyl);    -   R_(3′) is H, or halogen;        -   R′ is H, C₁-C₆ alkyl, phenyl(C₁-C₄)alkyl, C₁-C₆ alkanoyl,            phenyl(C₁-C₄)alkanoyl, pyridyl(C₁-C₄)alkyl, —SO₂-alkyl,            —SO₂-phenyl, —SO₂-pyridyl, pyridyl(C₁-C₆)alkanoyl, wherein            the alkyl portion of the alkyl and alkanoyl groups are            optionally substituted with halogen or C₁-C₄ alkoxy,            -   wherein the phenyl and pyridyl groups are optionally                substituted with C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,                CF₃, OCF₃;        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 6A. Compounds according to embodiment 6, wherein

-   -   R₁ is C₁-C₈ hydroxyalkyl. In one aspect, R₁ is C₂-C₆        hydroxyalkyl. In another aspect, R₁ is a C₃-C₆ hydroxyalkyl. In        still another aspect, R₁ is a C₅-C₆ hydroxyalkyl. In another        aspect, R₁ is a C₇-C₈ hydroxyalkyl. In yet another aspect, R₁ is

Embodiment 6B. Compounds according to embodiment 6, wherein

-   -   R₁ is C₁-C₈ alkyl. In another aspect, R₁ is a C₃-C₆ alkyl. In        still another aspect, R₁ is a C₅-C₆ alkyl. In another aspect, R₁        is C₅-C₈ alkyl. In still another aspect, R₁ is C₇-C₈ alkyl.

Embodiment 6C. Compounds according to either Embodiment 6A or Embodiment6B, wherein R₂ is C₁-C₈ alkyl. In another aspect, the R₂ is C₂-C₈ alkyl.In still another aspect, R₂ is C₂-C₆ alkyl. In yet another aspect, R₂ isC₃-C₄ alkyl (preferably, C₃ alkyl.) In another aspect, R₂ is C₁, C₃, orC₅ alkyl. In still another aspect, R₂ is n-propyl or isopropyl. Inanother aspect, R₂ is C₃-C₈ alkyl. In yet another aspect, R₂ is C₅-C₈alkyl. In still another aspect, R₂ is C₇-C₈ alkyl. In still anotheraspect, R₂ is C₅-C₇ alkyl.

Embodiment 6D. Compounds according to Embodiment 6C, wherein R₃ is H,halogen, methyl, methoxy, or CF₃;

-   -   R₄ is H, halogen (preferably Cl or F, more preferably Cl),        methoxy, methyl, or CF₃; and    -   R_(3′) is H, or halogen.

Embodiment 6E. Compounds according to Embodiment 6D, wherein R₃ andR_(3′) are both H; and R₄ is halogen (preferably Cl or F, morepreferably Cl), methoxy, methyl, or CF₃. In one aspect, R₄ is Cl. Inanother aspect, R₄ is methyl. In still another aspect, R₄ is CF₃.

In embodiment 7, the invention provides compounds according toembodiment 6, wherein

-   -   R₂ is C₁-C₈ alkyl which is optionally substituted with 1 or 2        phenyl groups, 2H-chromenyl, 1,2,3,4-tetrahydronaphthalenyl,        indolyl, 3,4-dihydronaphthalenyl, phenyl, naphthyl, C₃-C₈        cycloalkyl, benzofuranyl, indolyl, 1,4-benzodioxanyl,        1,3-benzodioxolyl, pyridyl, pyrimidyl, triazolyl, or CN,        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl (C₁-C₆) alkyl,            C₁-C₄ alkoxy optionally substituted with pyridyl, thiazolyl,            or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄            alkyl)-S(O)_(x)—R₂₅, or OH; wherein            -   x is 0, 1, or 2;            -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl.

Embodiment 7A. Compounds according to embodiment 7, wherein

-   -   R₂ is C₁-C₈ alkyl which is optionally substituted with        2H-chromenyl, 1,2,3,4-tetrahydronaphthalenyl, indolyl,        3,4-dihydronaphthalenyl, naphthyl, C₃-C₈ cycloalkyl,        benzofuranyl, indolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl,        pyridyl, triazolyl, or pyrimidyl, wherein the cyclic portions of        each of the above are optionally substituted with 1, 2, or 3        groups that are independently halogen, CO₂H, C₁-C₆        alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)        alkyl (C₁-C₆) alkyl, C₁-C₄ alkoxy optionally substituted with        pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,        —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   -   x is 0, 1, or 2;            -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl.

Embodiment 7B. Compounds according to embodiment 7, or embodiment 7A,wherein

-   -   R₂ is C₁-C₄ alkyl which is optionally substituted with        1,4-benzodioxanyl, or 1,3-benzodioxolyl,        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl (C₁-C₆) alkyl,            C₁-C₄ alkoxy optionally substituted with pyridyl, thiazolyl,            or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄            alkyl)-S(O)_(x)—R₂₅, or OH; wherein            -   x is 0, 1, or 2;            -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl. In another aspect, the                cyclic portions are unsubstituted.

Embodiment 7C. Compounds according to embodiment 7, or Embodiment 7A,wherein

-   -   R₂ is C₁-C₄ alkyl which is substituted with 2H-chromenyl,        1,2,3,4-tetrahydronaphthalenyl, indolyl,        3,4-dihydronaphthalenyl, naphthyl, or C₃-C₈ cycloalkyl,        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl (C₁-C₆) alkyl,            C₁-C₄ alkoxy optionally substituted with pyridyl, thiazolyl,            or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄            alkyl)-S(O)_(x)—R₂₅, or OH; wherein            -   x is 0, 1, or 2;            -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl. In another aspect, R₂₅                is C₁-C₆ alkyl or OH.

Embodiment 7d. Compounds according to Embodiment 7A, wherein R₂ is C₁-C₄alkyl which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl, 1,4-benzodioxanyl,1,3-benzodioxolyl, pyridyl, triazolyl, or pyrimidyl, each of which isunsubstituted.

Embodiment 7e. Compounds according to Embodiment 7A, wherein R₂ is C₁-C₂alkyl which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl, 1,4-benzodioxanyl,1,3-benzodioxolyl, pyridyl, or pyrimidyl, each of which isunsubstituted.

Embodiment 7f. Compounds according to Embodiment 7A, wherein R₂ is C₁-C₂alkyl which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,naphthyl, benzofuranyl, indolyl, 1,4-benzodioxanyl, or1,3-benzodioxolyl, each of which is unsubstituted.

In embodiment 8, the invention provides compounds according toembodiment 7, wherein

-   -   -   -   R₂ is C₁-C₈ alkyl which is optionally substituted with                phenyl group, benzofuranyl, 1,4-benzodioxanyl, or                1,3-benzodioxolyl,

        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl (C₁-C₆) alkyl,            C₁-C₄ alkoxy optionally substituted with pyridyl, thiazolyl,            or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄            alkyl)-S(O)_(x)—R₂₅, or OH; wherein            -   x is 0, 1, or 2;            -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl.

Embodiment 8A. Compounds according to embodiment 8, wherein

-   -   R₂ is C₁-C₈ alkyl substituted with phenyl, benzofuranyl,        1,4-benzodioxanyl, or 1,3-benzodioxolyl. In another aspect, the        alkyl group is C₁-C₄ alkyl. In still another aspect, the alkyl        group is C₂-C₅ alkyl. In yet still another aspect, the alkyl        group is C₃-C₅ alkyl. In another aspect, R₂ is C₃-C₈ alkyl. In        yet another aspect, R₂ is C₅-C₈ alkyl. In still another aspect,        R₂ is C₇-C₈ alkyl. In still another aspect, R₂ is C₅-C₇ alkyl.

Embodiment 8B. Compounds according to embodiment 8, wherein

-   -   R₂ is C₁-C₈ alkyl substituted with 1,4-benzodioxanyl, or        1,3-benzodioxolyl. In another aspect, the alkyl group is C₁-C₄        alkyl. In still another aspect, the alkyl group is C₂-C₅ alkyl.        In yet still another aspect, the alkyl group is C₃-C₅ alkyl. In        another aspect, R₂ is C₃-C₈ alkyl. In yet another aspect, R₂ is        C₅-C₈ alkyl. In still another aspect, R₂ is C₇-C₈ alkyl. In        still another aspect, R₂ is C₅-C₇ alkyl.

In embodiment 9, the invention provides compounds according toembodiment 8, wherein

-   -   R₂ is C₁-C₈ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl(C₁-C₆) alkyl, C₁-C₄        alkoxy optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 9A. Compounds according to embodiment 9, wherein

-   -   R₂ is C₁-C₄ alkyl (in another aspect, C₁-C₂ alkyl) substituted        with phenyl, wherein the phenyl is optionally substituted with        1, 2, or 3 groups that are independently halogen, CO₂H, C₁-C₆        alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)        alkyl (C₁-C₆) alkyl, C₁-C₄ alkoxy optionally substituted with        pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,        —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 9B. Compounds according to embodiment 9, wherein

-   -   R₂ is C₃-C₆ alkyl (in another aspect, C₃-C₅ alkyl) substituted        with phenyl, wherein the phenyl is optionally substituted with        1, 2, or 3 groups that are independently halogen, CO₂H, C₁-C₆        alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl,        —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄ alkoxy optionally        substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,        C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH;        wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 9C. Compounds according to embodiment 9, wherein

-   -   -   R₂ is C₅-C₈ alkyl (in another aspect, C₅-C₇ alkyl)            substituted with phenyl, wherein the phenyl is optionally            substituted with 1, 2, or 3 groups that are independently            halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄            alkoxy optionally substituted with pyridyl, thiazolyl, or            methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄            alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

In embodiment 10, the invention provides compounds according toembodiment 9, wherein

-   -   R₁ is C₁-C₈ hydroxyalkyl;    -   R₃ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, CN;    -   R₄ is H, halogen, C₁-C₄ alkoxy, CF₃, OCF₃, CN, phenyloxy,        —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₄ alkanoyl, pyridyl,        furanyl or thienyl, phenyl, or C₁-C₆ alkyl optionally        substituted with —CO₂—(C₁-C₆ alkyl);    -   R_(3′) is H, or halogen;        -   R′ is H, C₁-C₄ alkyl, benzyl, C₁-C₆ alkanoyl, phenyl(C₁-C₄)            alkanoyl, pyridyl(C₁-C₄)alkyl, —SO₂-alkyl, —SO₂-phenyl,            —SO₂-pyridyl, pyridyl(C₁-C₆)alkanoyl, wherein the alkyl            portion of the alkyl and alkanoyl groups are optionally            substituted with halogen or C₁-C₄ alkoxy,            -   wherein the phenyl and pyridyl groups are optionally                substituted with C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,                CF₃, OCF₃;        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

In embodiment 11, the invention provides compounds according toembodiment 10, wherein

-   -   R₁ is    -   R₃ is H, halogen, methyl, methoxy, CF₃, or CN;    -   R₄ is H, halogen, methyl, methoxy, CF₃, OCF₃, CN, —NHR′, or        —NR′R″;    -   R_(3′) is H, or halogen;        -   R′ is H, or C₁-C₄ alkyl; and        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 11A. Compounds according to embodiment 11, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄        alkoxy optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 11B. Compounds according to Embodiment 11A, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl isunsubstituted.

Embodiment 11C. Compounds according to embodiment 11A, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₃ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl.

Embodiment 11D. Compounds according to embodiment 11C, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₂ alkoxy, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl.

Embodiment 11D1. Compounds according to embodiment 11C, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 group that is halogen (in one aspect, F, Cl or Br), C₁-C₄ alkoxy(in one aspect, methoxy), or C₁-C₄ alkyl (in one aspect, methyl.) Inanother embodiment, the substituent is in the para position.

Embodiment 11E. Compounds according to embodiment 11D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 2 groups, one of which is a halogen or a methoxy group. In anotheraspect, the second group is a halogen or a methoxy group. In stillanother aspect, the phenyl is substituted with two halogens or twomethoxy groups.

Embodiment 11F. Compounds according to embodiment 11D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, CO₂H, C₁-C₆alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl,—C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, methoxy, or C₁-C₂ alkoxy optionallysubstituted with pyridyl, thiazolyl, or methyl thiazol-5-yl. In anotheraspect, the phenyl is di-substituted and one of the groups is methoxy.In yet another aspect, the phenyl is di-substituted, one of the groupsis methoxy and the other group is C₁-C₂ alkoxy substituted with pyridyl,thiazolyl, methyl thiazol-5-yl. In one aspect, the other group is C₁alkoxy substituted with pyridyl, or methyl thiazol-5-yl. In yet anotheraspect, the other group is C₂ alkoxy substituted with pyridyl, or methylthiazol-5-yl.

Embodiment 11G. Compounds according to Embodiment 11, wherein

-   -   R₂ is C₃-C₅ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄        alkoxy optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;            -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl,                phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or            -   R₂₆, R₂₇ and the nitrogen to which they are attached                represent pyrrolidinyl, piperidinyl, piperazinyl,                morpholinyl, or imidazolidinyl.

Embodiment 11H. Compounds according to Embodiment 11G, wherein

-   -   R₂ is C₃-C₄ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄        alkoxy optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 11I. Compounds according to Embodiment 11H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl isunsubstituted. In one aspect, the C₃ alkyl group is a straight chainedalkyl group. In another aspect, the C₄ alkyl group is a straight chainedC₃ alkyl group substituted with a methyl group.

Embodiment 11J. Compounds according to embodiment 11H, wherein

-   -   R₂ is C₃-C₄ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1, or 2 groups that are independently halogen,        CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₃ alkoxy optionally        substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,        C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH;        wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 11K. Compounds according to embodiment 11J, wherein

-   -   R₂ is C₃-C₄ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1, or 2 groups that are independently halogen,        CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₂ alkoxy, C₁-C₄ alkyl,        —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R26 and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 11L. Compounds according to embodiment 11K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 2 groups, one of which is a halogen or a methoxy group. In anotheraspect, the second group is a halogen or a methoxy group. In stillanother aspect, the phenyl is substituted with two halogens or twomethoxy groups.

Embodiment 11M. Compounds according to embodiment 11J, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, methoxy, or C₁-C₂alkoxy optionally substituted with pyridyl, thiazolyl, or methylthiazol-5-yl. In another aspect, the phenyl is di-substituted and one ofthe groups is methoxy. In yet another aspect, the phenyl isdi-substituted, one of the groups is methoxy and the other group isC₁-C₂ alkoxy substituted with pyridyl, thiazolyl, methyl thiazol-5-yl.In one aspect, the other group is C₁ alkoxy substituted with pyridyl, ormethyl thiazol-5-yl. In yet another aspect, the other group is C₂ alkoxysubstituted with pyridyl, or methyl thiazol-5-yl.

Embodiment 11N. Compounds according to any one of embodiments 11A, 11B,11C, 11D, 11E, 11F, 11G, 11H, 11I, 11J, 11K, or 11L wherein R₃ is H, orhalogen; R₄ is halogen, methyl, CF₃, or methoxy; and R_(3′) is H, orhalogen.

Embodiment 11O. Compounds according to embodiment 11N, wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl), methyl of CF₃;and R_(3′) is H. In another aspect, R₄ is methyl. In still anotheraspect, R₄ is CF₃. In yet another aspect, R₄ is Cl.

In embodiment 12, the invention provides compounds according toembodiment 5, wherein R₁ is C₁-C₈ alkyl;

-   -   R₂ is C₁-C₈ alkyl substituted with a phenyl group, benzofuranyl,        1,4-benzodioxanyl, or 1,3-benzodioxolyl, wherein the phenyl        group is optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄        alkoxy optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl;    -   R₃ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, CN;    -   R₄ is H, halogen, C₁-C₄ alkoxy, CF₃, OCF₃, CN, phenyloxy,        —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₄ alkanoyl, pyridyl,        furanyl or thienyl, phenyl, or C₁-C₄ alkyl optionally        substituted with —CO₂—(C₁-C₆ alkyl);    -   R_(3′) is H, or halogen;        -   R′ is H, C₁-C₄ alkyl, benzyl, C₁-C₆ alkanoyl, phenyl(C₁-C₄)            alkanoyl, pyridyl(C₁-C₄)alkyl, —SO₂-alkyl, —SO₂-phenyl,            —SO₂-pyridyl, pyridyl(C₁-C₆)alkanoyl, wherein the alkyl            portion of the alkyl and alkanoyl groups are optionally            substituted with halogen or C₁-C₄ alkoxy,            -   wherein the phenyl and pyridyl groups are optionally                substituted with C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,                CF₃, OCF₃;        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

In embodiment 13, the invention provides compounds according toembodiment 12, wherein

-   -   R₁ is C₂-C₈ alkyl;    -   R₃ is H, halogen, methyl, methoxy, CF₃, or CN;    -   R₄ is halogen, methyl, methoxy, CF₃, OCF₃, CN, —NHR′, or —NR′R″;    -   R_(3′) is H, or halogen;        -   R′ is H, or C₁-C₄ alkyl; and        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 13A. Compounds according to embodiment 13, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄        alkoxy optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 13B. Compounds according to Embodiment 13A, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl isunsubstituted.

Embodiment 13C. Compounds according to embodiment 13A, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₃ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 13D. Compounds according to embodiment 13C, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1, or 2 groups that are independently halogen,        CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₂ alkoxy, C₁-C₄ alkyl,        —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 13E. Compounds according to embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 2 methoxy groups.

Embodiment 13E1. Compounds according to Embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, C₁-C₄ alkoxycarbonyl,—C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. Inanother aspect, the C₁-C₄ alkoxycarbonyl is a methoxy carbonyl orethoxycarbonyl. More preferably, it is ethoxycarbonyl.

Embodiment 13E2. Compounds according to Embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, —C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. In anotheraspect, the phenyl group is substituted with 1 group selected that isCO₂H, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl.

Embodiment 13E3. Compounds according to embodiment 13D, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1 or 2 groups that are independently halogen,        CO₂H, C₁-C₄ alkoxycarbonyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 13E4. Compounds according to embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or OH.

Embodiment 13E5. Compounds according to Embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 13E6. Compounds according to Embodiment 13D, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1 or 2 groups that are independently        —S(O)_(x)—R₂₅, or —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅; wherein        -   x is 0, or 2; and        -   R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 13E7. Compounds according to Embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith NR₂₆R₂₇; wherein

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl (C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 13E8. Compounds according to Embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith NR₂₆R₂₇; wherein

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl.

Embodiment 13E9. Compounds according to Embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith NR₂₆R₂₇; wherein

-   -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 13F. Compounds according to embodiment 13D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, methoxy, or C₁-C₂ alkoxy optionallysubstituted with pyridyl, thiazolyl, methyl thiazol-5-yl. In anotheraspect, the phenyl is di-substituted and one of the groups is methoxy.In yet another aspect, the phenyl is di-substituted, one of the groupsis methoxy and the other group is C₁-C₂ alkoxy substituted with pyridyl,thiazolyl, or methyl thiazol-5-yl. In one aspect, the other group is C₁alkoxy substituted with pyridyl, or methyl thiazol-5-yl. In yet anotheraspect, the other group is C₂ alkoxy substituted with pyridyl, or methylthiazol-5-yl.

Embodiment 13G. Compounds according to Embodiment 13, wherein

-   -   R₂ is C₃-C₅ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄        alkoxy optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 13G1. Compounds according to Embodiment 13G, wherein

-   -   R₂ is C₃-C₅ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1 or 2 groups that are independently        —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl (C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 13G2. Compounds according to Embodiment 13G, wherein

-   -   R₂ is C₃-C₅ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1 or 2 groups that are independently        —S(O)_(x)—R₂₅, or —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅; wherein        -   x is 0, or 2; and        -   R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 13G3. Compounds according to Embodiment 13G, wherein

-   -   R₂ is C₃-C₅ alkyl substituted with phenyl, wherein the phenyl is        substituted with NR₂₆R₂₇; wherein        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 13G4. Compounds according to Embodiment 13G, wherein

-   -   R₂ is C₃-C₅ alkyl substituted with phenyl, wherein the phenyl is        substituted with NR₂₆R₂₇; wherein        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl.

Embodiment 13G5. Compounds according to Embodiment 13G, wherein R₂ isC₃-C₅ alkyl substituted with phenyl, wherein the phenyl is substitutedwith NR₂₆R₂₇; wherein

-   -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 13H. Compounds according to Embodiment 13G, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is optionallysubstituted with 1, 2, or 3 groups that are independently halogen, CO₂H,C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, or OH.

Embodiment 13I. Compounds according to Embodiment 13H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl isunsubstituted. In one aspect, the C₃ alkyl group is a straight chainedalkyl group. In another aspect, the C₄ alkyl group is a straight chainedC₃ alkyl group substituted with a methyl group.

Embodiment 13J. Compounds according to embodiment 13H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₃ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, or OH.

Embodiment 13K. Compounds according to embodiment 13J, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₂ alkoxy, C₁-C₄ alkyl, or OH.

Embodiment 13L. Compounds according to embodiment 13J, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 2 methoxy groups.

Embodiment 13L1. Compounds according to Embodiment 13K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, C₁-C₄ alkoxycarbonyl,—C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. Inanother aspect, the C₁-C₄ alkoxycarbonyl is a methoxy carbonyl orethoxycarbonyl. More preferably, it is ethoxycarbonyl.

Embodiment 13L2. Compounds according to Embodiment 13K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. In another aspect, the phenylgroup is substituted with 1 group selected that is CO₂H, —C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl.

Embodiment 13L3. Compounds according to embodiment 13K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, or OH.

Embodiment 13L4. Compounds according to embodiment 13K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or OH.

Embodiment 13M. Compounds according to embodiment 13J, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, methoxy, or C₁-C₂alkoxy optionally substituted with pyridyl, thiazolyl, methylthiazol-5-yl. In another aspect, the phenyl is di-substituted and one ofthe groups is methoxy. In yet another aspect, the phenyl isdi-substituted, one of the groups is methoxy and the other group isC₁-C₂ alkoxy substituted with pyridyl, thiazolyl, methyl thiazol-5-yl.In one aspect, the other group is C₁ alkoxy substituted with pyridyl, ormethyl thiazol-5-yl. In yet another aspect, the other group is C₂ alkoxysubstituted with pyridyl, or methyl thiazol-5-yl.

Embodiment 13N. Compounds according to embodiment 12, wherein R₂ isC₁-C₆ alkyl substituted with benzofuranyl, 1,4-benzodioxanyl, or1,3-benzodioxolyl. In another aspect, the alkyl group is C₁-C₄ alkyl. Instill another aspect, the alkyl group is C₂-C₅ alkyl. In yet stillanother aspect, the alkyl group is C₃-C₅ alkyl.

Embodiment 13O. Compounds according to any one of embodiments 13A, 13B,13C, 13D, 13E, 13E1, 13E2, 13E3, 13E4, 13E5, 13E6, 13E7, 13E8, 13E9,13F, 13G, 13H, 13H1, 13H2, 13H3, 13H4, 13H5, 13I, 13J, 13K, 13L, 13L1,13L2, 13L3, 13L4, 13M, or 13N wherein

-   -   R₃ is H, or halogen;    -   R₄ is halogen, methyl, CF₃, or methoxy; and    -   R_(3′) is H, or halogen.

Embodiment 13P. Compounds according to embodiment 13O, wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl), methyl, or CF₃;and R_(3′) is H. In another aspect, R₄ is methyl. In still anotheraspect, R₄ is CF₃. In yet another aspect, R₄ is Cl.

In embodiment 14, the invention provides compounds according toembodiment 6, wherein

-   -   R₂ is C₃-C₈ alkenyl, optionally substituted with 1 or 2 groups        that are independently phenyl, halogen, 2H-chromenyl,        1,2,3,4-tetrahydronaphthalenyl, indolyl,        3,4-dihydronaphthalenyl, naphthyl, C₃-C₈ cycloalkyl,        benzofuranyl, indolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl,        pyridyl, C₁-C₄ alkyl, halogen, —CO₂—(C₁-C₄ alkyl), pyrazolyl,        imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl,        thiadiazolyl, triazolyl, or pyrimidyl;        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄            alkoxy optionally substituted with pyridyl, thiazolyl, or            methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄            alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 14A. Compounds according to embodiment 14, wherein R₂ isC₃-C₈ alkenyl, which is optionally substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl, 1,4-benzodioxanyl,1,3-benzodioxolyl, pyridyl, triazolyl, or pyrimidyl; wherein the cyclicportions of each of the above are optionally substituted with 1, 2, or 3groups that are independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl,—C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄alkoxy optionally substituted with pyridyl, thiazolyl, or methylthiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅,or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

In another aspect, R₂ is C₃-C₆ alkenyl, which is optionally substitutedas above. In yet another aspect, R₂ is C₃-C₅ alkenyl, which isoptionally substituted as above. In another aspect, R₂ is C₄-C₇ alkenyl,which is optionally substituted as above.

Embodiment 14B. Compounds according to embodiment 14, wherein R₂ isC₃-C₈ alkenyl, which is substituted with 1 or 2 groups which areindependently C₁-C₄ alkyl, halogen, —CO₂—(C₁-C₄ alkyl), pyrazolyl,imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl,pyridyl, triazolyl, or pyrimidyl; wherein the cyclic portions of each ofthe above are optionally substituted with 1, or 2 groups that areindependently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxyoptionally substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl) -S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

In another aspect, R₂ is C₃-C₆ alkenyl, which is optionally substitutedas above. In yet another aspect, R₂ is C₃-C₅ alkenyl, which isoptionally substituted as above. In another aspect, the C₃-C₅ alkenyl issubstituted with a halogen (preferably Cl or Br.) In still anotheraspect, R₂ is C₄-C₇ alkenyl, which is optionally substituted as above.In another aspect, the C₄-C₇ alkenyl is substituted with a halogen(preferably Cl or Br.)

Embodiment 14C. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl, wherein the cyclic portions of each of the above areoptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 14D. Compounds according to embodiment 14, wherein R₂ isC₃-C₄ alkenyl, which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl.

Embodiment 14E. Compounds according to embodiment 14, wherein R₂ isC₃-C₄ alkenyl, which substituted with 1,2,3,4-tetrahydronaphthalenyl,3,4-dihydronaphthalenyl, or naphthyl.

Embodiment 14F. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with C₃-C₈ cycloalkyl. In another aspect, theC₃-C₈ cycloalkyl group is substituted with one or two methyl groups. Instill another aspect, the C₃-C₈ cycloalkyl group is substituted withonly —CH₂—OH. In yet still another aspect, the C₃-C₈ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH.

Embodiment 14G. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with C₃-C₆ cycloalkyl. In another aspect, theC₃-C₆ cycloalkyl group is substituted with one or two methyl groups. Instill another aspect, the C₃-C₆ cycloalkyl group is substituted withonly —CH₂—OH. In yet still another aspect, the C₃-C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH.

Embodiment 14H. Compounds according to embodiment 14, wherein R₂ isC₃-C₄ alkenyl, substituted with C₅-C₆ cycloalkyl. In another aspect, theC₅-C₆ cycloalkyl group is substituted with one or two methyl groups. Instill another aspect, the C₅-C₆ cycloalkyl group is substituted withonly —CH₂—OH. In yet still another aspect, the C₅-C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH. In one aspect, themethyl group and the —CH₂—OH group are in a 1, 2 relationship relativeto each other. In another aspect, the methyl group and the —CH₂—OH groupare in a 1, 3 relationship relative to each other.

Embodiment 14I. Compounds according to embodiment 14, wherein R₂ isC₃-C₄ alkenyl, substituted with C₆ cycloalkyl. In another aspect, the C₆cycloalkyl group is substituted with one or two methyl groups. In stillanother aspect, the C₆ cycloalkyl group is substituted with only—CH₂—OH. In yet still another aspect, the C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH. In one aspect, themethyl group and the —CH₂—OH group are in a 1, 2 relationship relativeto each other. In another aspect, the methyl group and the —CH₂—OH groupare in a 1, 3 relationship relative to each other.

Embodiment 14J. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with 2H-chromenyl, indolyl, benzofuranyl,1,4-benzodioxanyl, 1,3-benzodioxolyl, pyridyl, triazolyl, or pyrimidyl;wherein the cyclic portions of each of the above are optionallysubstituted with 1, 2, or 3 groups that are independently halogen, CO₂H,C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

In another aspect, the cyclic portion of R₂ is not substituted.

Embodiment 14K. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with 2H-chromenyl, indolyl, benzofuranyl,1,4-benzodioxanyl, or 1,3-benzodioxolyl; wherein the cyclic portions ofeach of the above are optionally substituted with 1, 2, or 3 groups thatare independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxyoptionally substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

In another aspect, the cyclic portion of R₂ is not substituted.

Embodiment 14L. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with pyridyl, or pyrimidyl; wherein thecyclic portions of each of the above are optionally substituted with 1,2, or 3 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ and the nitrogen to        which they are attached represent pyrrolidinyl, piperidinyl,        piperazinyl, morpholinyl, or imidazolidinyl. In another aspect,        the cyclic portion of R₂ is not substituted. In still another        aspect, the pyridyl group is pyrid-2-yl, pyrid-3-yl, which is        optionally substituted with one group that is methyl, methoxy,        or halogen.

Embodiment 14M. Compounds according to embodiment 14, wherein

-   -   R₂ is C₃-C₈ alkenyl. In another aspect, R₂ is C₃-C₆ alkenyl. In        still another aspect, R₂ is C₃-C₅ alkenyl. In yet still another        aspect, R₂ is C₄-C₆ alkenyl.

Embodiment 14N. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with benzofuranyl, 1,4-benzodioxanyl, or1,3-benzodioxolyl.

Embodiment 14N1. Compounds according to Embodiment 14N, wherein R₂ isC₃-C₆ alkenyl, substituted with 1,4-benzodioxanyl, or 1,3-benzodioxolyl.

Embodiment 14N2. Compounds according to Embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with halogen or —CO₂—(C₁-C₃ alkyl).

Embodiment 14N3. Compounds according to embodiment 14, wherein R₂ isC₃-C₆ alkenyl, substituted with at least one triazolyl, which isoptionally substituted as described in embodiment 14. In another aspect,the triazolyl group is unsubstituted. In still another aspect, thetriazolyl group is substituted with only one group.

Embodiment 14O. Compounds according to embodiments 14 14A, 14B, 14C,14D, 14E, 14F, 14,G, 14H, 14I, 14J, 14K, 14L, 14M, 14N, 14N1, 14N2, or14N3, wherein R₁ is C₁-C₈ alkyl. In another aspect, R₁ is C₂-C₈ alkyl.In still another aspect, R₁ is C₃-C₆ alkyl. In yet still another aspect,R₁ is C₃-C₅ alkyl. In another aspect, R₁ is C₆-C₈ alkyl. In stillanother aspect, C₇-C₈ alkyl.

Embodiment 14P. Compounds according to embodiments 14 14A, 14B, 14C,14D, 14E, 14F, 14,G, 14H, 14I, 14J, 14K, 14L, 14M, or 14N wherein R₁ isC₁-C₈ hydroxyalkyl. In another aspect, R₁ is C₂-C₆ hydroxyalkyl. Instill another aspect, R₁ is C₃-C₆ hydroxyalkyl. In yet still anotheraspect, R₁ is C₄-C₆ hydroxyalkyl. In yet still another aspect, R₁ isC₅-C₆ hydroxyalkyl. In another aspect, R₁ is C₇-C₈ hydroxyalkyl.

Embodiment 14Q. Compounds according to Embodiment 14N, wherein

-   -   R₁ is

Embodiment 14R. Compounds according to Embodiment 14O, Embodiment 14P,or Embodiment 14Q wherein R₃ is H, or halogen;

-   -   R₄ is halogen, methyl, CF₃, or methoxy; and R_(3′) is H, or        halogen.

Embodiment 14S. Compounds according to Embodiment 14O Embodiment 14P, orEmbodiment 14Q wherein R₃ is H; R₄ is halogen (preferably F or Cl, morepreferably Cl), methyl or CF₃; and R_(3′) is H. In another aspect, R₄ ismethyl. In still another aspect, R₄ is CF₃. In yet another aspect, R₄ isCl.

In embodiment 15, the invention provides compounds according toembodiment 14, wherein

-   -   R₂ is C₃-C₆ alkenyl, optionally substituted with 1 or 2 groups        that are phenyl, halogen, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, or        pyrimidyl; wherein the phenyl group is optionally substituted        with 1, 2, or 3 groups that are independently halogen, CO₂H,        C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally        substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,        C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH;        wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl (C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 15A. Compounds according to embodiment 15, wherein R₂ isC₃-C₆ alkenyl substituted with phenyl; wherein the phenyl group isoptionally substituted with 1, 2, or 3 groups that are independentlyhalogen (in one aspect, F or Cl), CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy,C₁-C₄ alkyl, or OH.

Embodiment 15B. Compounds according to embodiment 15, wherein R₂ isC₃-C₆ alkenyl.

Embodiment 15C. Compounds according to embodiment 15, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group isoptionally substituted with 1 or 2 groups that are independently halogen(in one aspect, F or Cl), CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy, orC₁-C₄ alkoxy substituted with pyridyl, thiazolyl, methyl thiazol-5-yl,—S(O)_(x)—R₂₅, or —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 15D. Compounds according to embodiment 15, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group issubstituted with 2 methoxy groups. In one aspect, the methoxy groups arein a 1, 2 relationship relative to each other. In another aspect, themethoxy groups are in a 1, 3 relationship relative to each other.

Embodiment 15D1. Compounds according to Embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, C₁-C₄ alkoxycarbonyl,—C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. Inanother aspect, the C₁-C₄ alkoxycarbonyl is a methoxy carbonyl orethoxycarbonyl. More preferably, it is ethoxycarbonyl.

Embodiment 15D2. Compounds according to Embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, —C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. In anotheraspect, the phenyl group is substituted with 1 group selected that isCO₂H, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl.

Embodiment 15D3. Compounds according to embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen (in one aspect, F, Cl,or Br in another aspect, Br or F), CO₂H, C₁-C₄ alkoxycarbonyl, or OH. Inone aspect, the halogen is meta relative to the point of attachment ofthe alkenyl group to the phenyl group. In another aspect, the halogen isortho relative to the point of attachment of the alkenyl group to thephenyl group.

Embodiment 15D4. Compounds according to embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen (in one aspect, F, Cl,or Br in another aspect, Br or F), —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or OH. In one aspect, the halogen ismeta relative to the point of attachment of the alkenyl group to thephenyl group. In another aspect, the halogen is ortho relative to thepoint of attachment of the alkenyl group to the phenyl group.

Embodiment 15D5. Compounds according to embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 15D6. Compounds according to embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 15D7. Compounds according to embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 group that is NR₂₆R₂₇; wherein

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl.

Embodiment 15D8. Compounds according to embodiment 15C, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 group that is NR₂₆R₂₇; wherein

-   -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 15E. Compounds according to embodiment 15, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group issubstituted with 1 methoxy group. In another aspect, the phenyl group issubstituted with 1 methoxy group and C₂-C₃ alkoxy substituted withpyridyl, thiazolyl, methyl thiazol-5-yl.

Embodiment 15F. Compounds according to embodiment 15, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, which is unsubstituted.

Embodiment 15G. Compounds according to embodiment 15, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group issubstituted with 1 halogen and 1 methoxy group.

Embodiment 15G1. Compounds according to embodiment 15, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, CO₂H, or C₁-C₄alkoxycarbonyl.

Embodiment 15H. Compounds according to embodiment 15, wherein

-   -   R₂ is        wherein R₁₀ is C₁-C₄ alkyl (in one aspect, methyl), halogen (in        one aspect, Cl or Br), phenyl, pyridyl, pyrazolyl, imidazolyl,        oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl; and        the phenyl group is unsubstituted or substituted as in any one        of Embodiments 15A, 15C, 15D, 15D1, 15D2, 15D3, 15D4, 15D5,        15D6, 15D7, 15D8, 15E, or 15G. In one aspect, R₁₀ is methyl        chloro or bromo. In another aspect, R₁₀ is phenyl or pyridyl. In        still another aspect, R₁₀ is pyrazolyl, oxazolyl, isoxazolyl,        oxadiazolyl, thiazolyl, or thiadiazolyl. In yet another aspect,        R₁₀ is pyrazolyl or imidazolyl. In another aspect, R₁₀ is        oxazolyl, isoxazolyl, or oxadiazolyl. In another aspect, R₁₀ is        thiazolyl or thiadiazolyl.

Embodiment 15I. Compounds according to any one of embodiments 15, 15A,15B, 15C, 15D, 15D1, 15D2, 15D3, 15D4, 15D5, 15D6, 15D7, 15D8, 15E, 15F,15G, 15G1, or 15H wherein R₁ is C₁-C₈ hydroxyalkyl. In another aspect,R₁ is a C₃-C₆ hydroxyalkyl. In still another aspect, R₁ is a C₅-C₆hydroxyalkyl. In another aspect, R₁ is C₇-C₈ hydroxyalkyl.

Embodiment 15J. Compounds according to Embodiment 15I, wherein

-   -   R₁ is

Embodiment 15K. Compounds according to any one of embodiments 15, 15A,15B, 15C, 15D, 15E, 15F, 15G, 15G1, or 15H wherein R₁ is C₁-C₈ alkyl. Inanother aspect, R₁ is a C₃-C₆ alkyl. In still another aspect, R₁ is aC₅-C₆ alkyl. In another aspect, R₁ is C₇-C₈ alkyl.

Embodiment 15L. Compounds according to any one of embodiments 15, 15A,15B, 15C, 15D, 15D1, 15D2, 15D3, 15D4, 15E, 15F, 15G, 15G1, 15H, 15I,15J, or 15K, wherein

-   -   R₃ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, CN;    -   R₄ is H, halogen, C₁-C₄ alkoxy, CF₃, OCF₃, CN, phenyloxy,        —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₄ alkanoyl, pyridyl,        furanyl or thienyl, phenyl, or C₁-C₄ alkyl optionally        substituted with —CO₂—(C₁-C₆ alkyl);    -   R_(3′) is H, or halogen;        -   R′ is H, C₁-C₄ alkyl, benzyl, C₁-C₆ alkanoyl,            phenyl(C₁-C₄)alkanoyl, pyridyl(C₁-C₄)alkyl, —SO₂-alkyl,            —SO₂-phenyl, —SO₂-pyridyl, pyridyl(C₁-C₆)alkanoyl, wherein            the alkyl portion of the alkyl and alkanoyl groups are            optionally substituted with halogen or C₁-C₄ alkoxy,            -   wherein the phenyl and pyridyl groups are optionally                substituted with C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,                CF₃, OCF₃;        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 15M. Compounds according to Embodiment 15L, wherein

-   -   R₃ is H., halogen, methyl, methoxy, CF₃, or CN;    -   R₄ is halogen, methyl, methoxy, CF₃, OCF₃, CN, —NHR′, or —NR′R″;        and    -   R_(3′) is H, or halogen;        -   R′ is H, or C₁-C₄ alkyl; and        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 15N. Compounds according to Embodiment 15M wherein R₃ is H,or halogen; R₄ is halogen, methyl, CF₃, or methoxy; and R_(3′) is H, orhalogen.

Embodiment 15O. Compounds according to Embodiment 15N wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl), methyl or CF₃;and R_(3′) is H. In another aspect, R₄ is methyl. In still anotheraspect, R₄ is CF₃. In yet another aspect, R₄ is Cl.

In embodiment 16, the invention provides compounds according to FormulaI, wherein

-   -   R₁ is C₃-C₈ cycloalkyl optionally substituted with 1 or 2 groups        that are independently C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, or OH;        or    -   R₁ is heterocycloalkyl or heterocycloalkyl(C₁-C₄)alkyl wherein        the heterocycloalkyl group is piperidinyl, pyrrolidinyl,        tetrahydrofuranyl, pyrazolyl, or morpholinyl, wherein the        heterocycloalkyl groups are optionally substituted with 1 or 2        groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl,        phenyl(C₁-C₄)alkyl, OH, halogen, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl,        or C₁-C₄ alkoxycarbonyl; or    -   R₁ is heteroaryl(C₁-C₄)alkyl, wherein the heteroaryl group is        pyridyl, pyrimidyl, furanyl, or thienyl and the heteroaryl group        is optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄        alkyl, C₁-C₄ alkoxy or OH.

Embodiment 16A. Compounds according to any one of embodiments 15H, 15I,15J, 15K, 15L, 15M, 15N, 15O, or 16, wherein R₁₀ is methyl, chloro, orbromo.

In embodiment 17, the invention provides compounds according toembodiment 16, wherein

-   -   R₂ is C₁-C₈ alkyl, or C₂-C₈ alkenyl, each of which is optionally        substituted with 1 or 2 groups that are independently,        2H-chromenyl, 1,2,3,4-tetrahydronaphthalenyl, indolyl,        3,4-dihydronaphthalenyl, phenyl, naphthyl, C₃-C₈ cycloalkyl,        benzofuranyl, indolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl,        pyridyl, pyrimidyl, C₁-C₄ alkyl, halogen, pyrazolyl, imidazolyl,        oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl,        furanyl, triazolyl, or CN,        -   wherein the cyclic portions of each of the above are            optionally substituted with 1, 2, or 3 groups that are            independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,            —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄            alkoxy, C₁-C₄ alkoxy optionally substituted with pyridyl,            thiazolyl, or methyl thiazol-5-yl, NO₂, C₁-C₄ alkyl,            —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17A. Compounds according to embodiment 17, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄        alkoxy, C₁-C₄ alkoxy optionally substituted with pyridyl,        thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅,        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17B. Compounds according to Embodiment 17A, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl isunsubstituted.

Embodiment 17C. Compounds according to embodiment 17A, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1, or 2 groups that are independently halogen,        CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy, C₁-C₃ alkoxy        optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R27 are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17C1. Compounds according to embodiment 17C, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R26 and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17C2. Compounds according to embodiment 17C, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is        0, 1, or 2; R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 17C3. Compounds according to embodiment 17C, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 group that is NR₂₆R₂₇; wherein R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl.

Embodiment 17C4. Compounds according to embodiment 17C, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 group that is NR₂₆R₂₇; wherein

-   -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 17D. Compounds according to embodiment 17C, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy, C₁-C₂ alkoxy, C₁-C₄alkyl, or OH.

Embodiment 17E. Compounds according to embodiment 17D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 2 methoxy groups.

Embodiment 17E1. Compounds according to Embodiment 17D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, C₁-C₄ alkoxycarbonyl,—C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. Inanother aspect, the C₁-C₄ alkoxycarbonyl is a methoxy carbonyl orethoxycarbonyl. More preferably, it is ethoxycarbonyl.

Embodiment 17E2. Compounds according to Embodiment 17D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, —C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. In anotheraspect, the phenyl group is substituted with 1 group selected that isCO₂H, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl.

Embodiment 17E3. Compounds according to embodiment 17D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, or OH.

Embodiment 17E4. Compounds according to embodiment 17D, wherein R₂ isC₁-C₂ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, —C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or OH.

Embodiment 17F. Compounds according to embodiment 17D, wherein

-   -   R₂ is C₁-C₂ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1, or 2 groups that are independently halogen,        methoxy, or C₁-C₂ alkoxy optionally substituted with pyridyl,        thiazolyl, methyl thiazol-5-yl. In another aspect, the phenyl is        di-substituted and one of the groups is methoxy. In yet another        aspect, the phenyl is di-substituted, one of the groups is        methoxy and the other group is C₁-C₂ alkoxy substituted with        pyridyl, thiazolyl, methyl thiazol-5-yl. In one aspect, the        other group is C₁ alkoxy substituted with pyridyl, or methyl        thiazol-5-yl. In yet another aspect, the other group is C₂        alkoxy substituted with pyridyl, or methyl thiazol-5-yl.

Embodiment 17G. Compounds according to Embodiment 17, wherein

-   -   R₂ is C₃-C₅ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄        alkoxy, C₁-C₄ alkoxy optionally substituted with pyridyl,        thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅,        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17H. Compounds according to Embodiment 17G, wherein

-   -   R₂ is C₃-C₄ alkyl substituted with phenyl, wherein the phenyl is        optionally substituted with 1, 2, or 3 groups that are        independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄        alkoxy, C₁-C₄ alkoxy optionally substituted with pyridyl,        thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅,        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17H1. Compounds according to embodiment 17H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17H2. Compounds according to embodiment 17H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 17H3. Compounds according to embodiment 17H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 group that is NR₂₆R₂₇; wherein R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl.

Embodiment 17H4. Compounds according to embodiment 17H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 group that is NR₂₆R₂₇; wherein R₂₆, R₂₇ and the nitrogen to whichthey are attached represent pyrrolidinyl, piperidinyl, piperazinyl,morpholinyl, or imidazolidinyl.

Embodiment 17I. Compounds according to Embodiment 17H, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl isunsubstituted. In one aspect, the C₃ alkyl group is a straight chainedalkyl group. In another aspect, the C₄ alkyl group is a straight chainedC₃ alkyl group substituted with a methyl group.

Embodiment 17J. Compounds according to embodiment 17H, wherein

-   -   R₂ is C₃-C₄ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1, or 2 groups that are independently halogen,        CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy, C₁-C₃ alkoxy        optionally substituted with pyridyl, thiazolyl, or methyl        thiazol-5-yl, C₁-C₄ alkyl, or OH.

Embodiment 17K. Compounds according to embodiment 17J, wherein

-   -   R₂ is C₃-C₄ alkyl substituted with phenyl, wherein the phenyl is        substituted with 1, or 2 groups that are independently halogen,        CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy, C₁-C₂ alkoxy,        C₁-C₄ alkyl, or OH.

Embodiment 17K1. Compounds according to Embodiment 17K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, C₁-C₄ alkoxycarbonyl,—C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. Inanother aspect, the C₁-C₄ alkoxycarbonyl is a methoxy carbonyl orethoxycarbonyl. More preferably, it is ethoxycarbonyl.

Embodiment 17K2. Compounds according to Embodiment 17K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently CO₂H, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. In another aspect, the phenylgroup is substituted with 1 group selected that is CO₂H, —C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl.

Embodiment 17K3. Compounds according to embodiment 17K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, or OH.

Embodiment 17K4. Compounds according to embodiment 17K, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1 or 2 groups that are independently halogen, —C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or OH.

Embodiment 17L. Compounds according to embodiment 17J, wherein

-   -   R₂ is C₃-C₄ alkyl substituted with phenyl, wherein the phenyl is        substituted with 2 methoxy groups.

Embodiment 17M. Compounds according to embodiment 17J, wherein R₂ isC₃-C₄ alkyl substituted with phenyl, wherein the phenyl is substitutedwith 1, or 2 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O) NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, methoxy, or C₁-C₂ alkoxy optionallysubstituted with pyridyl, thiazolyl, methyl thiazol-5-yl. In anotheraspect, the phenyl is di-substituted and one of the groups is methoxy.In yet another aspect, the phenyl is di-substituted, one of the groupsis methoxy and the other group is C₁-C₂ alkoxy substituted with pyridyl,thiazolyl, methyl thiazol-5-yl. In one aspect, the other group is C₁alkoxy substituted with pyridyl, or methyl thiazol-5-yl. In yet anotheraspect, the other group is C₂ alkoxy substituted with pyridyl, or methylthiazol-5-yl.

Embodiment 17N. Compounds according to embodiment 17, wherein R₂ isC₁-C₆ alkyl substituted with 1,4-benzodioxanyl, or 1,3-benzodioxolyl. Inanother aspect, the alkyl group is C₁-C₄ alkyl. In still another aspect,the alkyl group is C₂-C₅ alkyl. In yet still another aspect, the alkylgroup is C₃-C₅ alkyl. In another aspect, R₂ is C₃-C₈ alkyl. In yetanother aspect, R₂ is C₅-C₈ alkyl. In still another aspect, R₂ is C₇-C₈alkyl. In still another aspect, R₂ is C₅-C₇ alkyl.

Embodiment 17O. Compounds according to embodiment 17, wherein R₂ isC₃-C₈ alkenyl, which is optionally substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl, 1,4-benzodioxanyl,1,3-benzodioxolyl, pyridyl, or pyrimidyl; wherein the cyclic portions ofeach of the above are optionally substituted with 1, 2, or 3 groups thatare independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxyoptionally substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; whereinx is 0, 1, or 2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ areindependently H, C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl;or R₂₆, R₂₇ and the nitrogen to which they are attached representpyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl.

Embodiment 17P. Compounds according to embodiment 17, wherein R₂ isC₃-C₈ alkenyl, which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl, 1,4-benzodioxanyl,1,3-benzodioxolyl, pyridyl, or pyrimidyl; wherein the cyclic portions ofeach of the above are optionally substituted with 1, 2, or 3 groups thatare independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxyoptionally substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,C₁-C₄ alkyl, or OH.

Embodiment 17Q. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl, which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl, wherein the cyclic portions of each of the above areoptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently        H, C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R26,        R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 17Q1. Compounds according to embodiment 17Q, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl, wherein the cyclic portions of each of the above areoptionally substituted with 1 or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17Q2. Compounds according to embodiment 17Q, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl, wherein the cyclic portions of each of the above areoptionally substituted with 1 or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 17Q3. Compounds according to embodiment 17Q, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl, wherein the cyclic portions of each of the above areoptionally substituted with 1 group that is NR₂₆R₂₇; wherein

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl.

Embodiment 17Q4. Compounds according to embodiment 17Q, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl, wherein the cyclic portions of each of the above areoptionally substituted with 1 group that is NR₂₆R₂₇; wherein R₂₆, R₂₇and the nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl.

Embodiment 17R. Compounds according to embodiment 17, wherein R₂ isC₃-C₄ alkenyl, which is substituted with 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, 3,4-dihydronaphthalenyl, naphthyl, orC₃-C₈ cycloalkyl.

Embodiment 17S. Compounds according to embodiment 17, wherein R₂ isC₃-C₄ alkenyl, which is substituted with 1,2,3,4-tetrahydronaphthalenyl,3,4-dihydronaphthalenyl, or naphthyl.

Embodiment 17S1. Compounds according to embodiment 17, wherein R₂ isC₃-C₅ alkenyl, substituted with naphthyl, which is optionallysubstituted with two groups that are independently C₁-C₄ alkyl, C₁-C₄alkoxy, or halogen. In another aspect, the naphthyl is unsubstituted.

Embodiment 17T. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl, substituted with C₃-C₈ cycloalkyl. In another aspect, theC₃-C₈ cycloalkyl group is substituted with one or two methyl groups. Instill another aspect, the C₃-C₈ cycloalkyl group is substituted withonly —CH₂—OH. In yet still another aspect, the C₃-C₈ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH.

Embodiment 17U. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl, substituted with C₃-C₆ cycloalkyl. In another aspect, theC₃-C₆ cycloalkyl group is substituted with one or two methyl groups. Instill another aspect, the C₃-C₆ cycloalkyl group is substituted withonly —CH₂—OH. In yet still another aspect, the C₃-C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH.

Embodiment 17V. Compounds according to embodiment 17, wherein R₂ isC₃-C₄ alkenyl, substituted with C₅-C₆ cycloalkyl. In another aspect, theC₅-C₆ cycloalkyl group is substituted with one or two methyl groups. Instill another aspect, the C₅-C₆ cycloalkyl group is substituted withonly —CH₂—OH. In yet still another aspect, the C₅-C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH. In one aspect, themethyl group and the —CH₂—OH group are in a 1, 2 relationship relativeto each other. In another aspect, the methyl group and the —CH₂—OH groupare in a 1, 3 relationship relative to each other.

Embodiment 17W. Compounds according to embodiment 17, wherein R₂ isC₃-C₄ alkenyl, substituted with C₆ cycloalkyl. In another aspect, the C₆cycloalkyl group is substituted with one or two methyl groups. In stillanother aspect, the C₆ cycloalkyl group is substituted with only—CH₂—OH. In yet still another aspect, the C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH. In one aspect, themethyl group and the —CH₂—OH group are in a 1, 2 relationship relativeto each other. In another aspect, the methyl group and the —CH₂—OH groupare in a 1, 3 relationship relative to each other.

Embodiment 17X. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl, substituted with 2H-chromenyl, indolyl, benzofuranyl,1,4-benzodioxanyl, 1,3-benzodioxolyl, pyridyl, or pyrimidyl; wherein thecyclic portions of each of the above are optionally substituted with 1,2, or 3 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

In another aspect, the cyclic portion of R₂ is not substituted.

Embodiment 17Y. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl, substituted with 2H-chromenyl, indolyl, benzofuranyl,1,4-benzodioxanyl, or 1,3-benzodioxolyl; wherein the cyclic portions ofeach of the above are optionally substituted with 1, 2, or 3 groups thatare independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxyoptionally substituted with pyridyl, thiazolyl, or methyl thiazol-5-yl,C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

In another aspect, the cyclic portion of R₂ is not substituted.

Embodiment 17Y1. Compounds according to embodiment 17Y, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl, indolyl,benzofuranyl, 1,4-benzodioxanyl, or 1,3-benzodioxolyl; wherein thecyclic portions of each of the above are optionally substituted with 1or 2 groups that are independently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17Y2. Compounds according to embodiment 17Y, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl, indolyl,benzofuranyl, 1,4-benzodioxanyl, or 1,3-benzodioxolyl; wherein thecyclic portions of each of the above are optionally substituted with 1or 2 groups that are independently —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 17Y3. Compounds according to embodiment 17Y, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl, indolyl,benzofuranyl, 1,4-benzodioxanyl, or 1,3-benzodioxolyl; wherein thecyclic portions of each of the above are optionally substituted with 1group that is NR₂₆R₂₇; wherein

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl.

Embodiment 17Y4. Compounds according to embodiment 17Y, wherein R₂ isC₃-C₅ alkenyl which is substituted with 2H-chromenyl, indolyl,benzofuranyl, 1,4-benzodioxanyl, or 1,3-benzodioxolyl; wherein thecyclic portions of each of the above are optionally substituted with 1group that is NR₂₆R₂₇; wherein

-   -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 17Z. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl, substituted with pyridyl, or pyrimidyl, wherein thecyclic portions of each of the above are optionally substituted with 1,2, or 3 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl. In anotheraspect, the cyclic portion of R₂ is not substituted.

Embodiment 17Z1. Compounds according to embodiment 17Z, wherein R₂ isC₃-C₅ alkenyl which is substituted with pyridyl, or pyrimidyl, whereinthe cyclic portions of each of the above are optionally substituted with1 or 2 groups that are independently —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or 2; R₂₅ is C₁-C₆ alkyl,OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ and the nitrogen to which theyare attached represent pyrrolidinyl, piperidinyl, piperazinyl,morpholinyl, or imidazolidinyl.

Embodiment 17Z2. Compounds according to embodiment 17Z, wherein R₂ isC₃-C₅ alkenyl which is substituted with pyridyl, or pyrimidyl, whereinthe cyclic portions of each of the above are optionally substituted with1 or 2 groups that are independently —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or 2; R₂₅ is C₁-C₆ alkyl,or OH.

Embodiment 17Z3. Compounds according to embodiment 17Z, wherein R₂ isC₃-C₅ alkenyl which is substituted with pyridyl, or pyrimidyl, whereinthe cyclic portions of each of the above are optionally substituted with1 group that is NR₂₆R₂₇; wherein

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl.

Embodiment 17Z4. Compounds according to embodiment 17Z, wherein R₂ isC₃-C₅ alkenyl which is substituted with pyridyl, or pyrimidyl, whereinthe cyclic portions of each of the above are optionally substituted with1 group that is NR₂₆R₂₇; wherein

-   -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 17Z5. Compounds according to embodiment 17Z, wherein R₂ isC₃-C₅ alkenyl which is substituted with pyridyl, or pyrimidyl, whereinthe cyclic portions of each of the above are optionally substituted withone halogen.

Embodiment 17AA. Compounds according to embodiment 17, wherein R₂ isC₃-C₈ alkenyl. In another aspect, R₂ is C₃-C₇ alkenyl. In still anotheraspect, R₂ is C₃-C₅ alkenyl. In yet still another aspect, R₂ is C₄-C₆alkenyl.

Embodiment 17BB. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl, substituted with 1,4-benzodioxanyl, or 1,3-benzodioxolyl.

Embodiment 17CC. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl substituted with phenyl; wherein the phenyl group isoptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, C₁-C₄ alkoxy, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein

-   -   x is 0, 1, or 2;    -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

In another aspect, the cyclic portion of R₂ is not substituted.

Embodiment 17CC1. Compounds according to embodiment 17CC, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the cyclic portions ofeach of the above are optionally substituted with 1 or 2 groups that areindependently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl.

Embodiment 17CC2. Compounds according to embodiment 17CC, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the cyclic portions ofeach of the above are optionally substituted with 1 or 2 groups that areindependently

-   -   —S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, or OH.

Embodiment 17CC3. Compounds according to embodiment 17CC, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the cyclic portions ofeach of the above are optionally substituted with 1 group that isNR₂₆R₂₇; wherein

-   -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl.

Embodiment 17CC4. Compounds according to embodiment 17CC, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl, wherein the cyclic portions ofeach of the above are optionally substituted with 1 group that isNR₂₆R₂₇; wherein

-   -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 17DD. Compounds according to embodiment 17, wherein R₂ isC₃-C₆ alkenyl.

Embodiment 17EE. Compounds according to embodiment 17, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group isoptionally substituted with 1 or 2 groups that are independentlyhalogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxy substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl.

Embodiment 17FF. Compounds according to embodiment 17, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group issubstituted with 2 methoxy groups. In one aspect, the methoxy groups arein a 1, 2 relationship relative to each other. In another aspect, themethoxy groups are in a 1, 3 relationship relative to each other.

Embodiment 17GG. Compounds according to embodiment 17, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group issubstituted with 1 methoxy group. In another aspect, the phenyl group issubstituted with 1 methoxy group and C₂-C₃ alkoxy substituted withpyridyl, thiazolyl, or methyl thiazol-5-yl.

Embodiment 17HH. Compounds according to embodiment 17, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl.

Embodiment 17II. Compounds according to embodiment 17, wherein R₂ isC₃-C₅ alkenyl substituted with phenyl; wherein the phenyl group issubstituted with 1 halogen and 1 methoxy group.

Embodiment 17JJ. Compounds according to embodiment 17, wherein R₂ is

wherein

-   -   R₁₀ is C₁-C₄ alkyl (in one aspect, methyl), halogen (in one        aspect, Cl or Br), phenyl, pyridyl, pyrazolyl, imidazolyl,        oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl; and        the phenyl group is unsubstituted or substituted as in any one        of Embodiments 17CC, 17CC1, 17CC2, 17CC3, 17CC4, 17EE, 17FF,        17GG, 17HH, or 17II. In one aspect, R₁₀ is methyl chloro or        bromo. In another aspect, R₁₀ is phenyl or pyridyl. In still        another aspect, R₁₀ is pyrazolyl, oxazolyl, isoxazolyl,        oxadiazolyl, thiazolyl, or thiadiazolyl. In yet another aspect,        R₁₀ is pyrazolyl or imidazolyl. In another aspect, R₁₀ is        oxazolyl, isoxazolyl, or oxadiazolyl. In another aspect, R₁₀ is        thiazolyl or thiadiazolyl.

Embodiment 17KK. Compounds according to any one of embodiments 15, 17A,17B, 17C, 17C1, 17C2, 17C3, 17C4, 17D, 17E, 17E1, 17E2, 17E3, 17E4, 17F,17G, 17H, 17H1, 17H2, 17H3, 17H4, 17I, 17J, 17K, 17L, 17M, 17N, 17O,17P, 17Q, 17Q1, 17Q2, 17Q3, 17Q4, 17R, 17S, 17T, 17U, 17V, 17W, 17X,17Y, 17Y1, 17Y2, 17Y3, 17Y4, 17Z, 17Z1, 17Z2, 17Z3, 17Z4, 17Z5, 17AA,17BB, 17CC, 17CC1, 17CC2, 17CC3, 17CC4, 17DD, 17EE, 17FF, 17GG, 17HH,17II, or 17JJ wherein

-   -   R₃ is H, halogen, C₁-C₄ alkyl, C1-C4 alkoxy, CF₃, CN;    -   R₄ is H, halogen, C₁-C₄ alkoxy, CF₃, OCF₃, CN, phenyloxy,        —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₄ alkanoyl, pyridyl,        furanyl or thienyl, phenyl, or C₁-C₄ alkyl optionally        substituted with —CO₂—(C₁-C₆ alkyl);    -   R_(3′) is H, or halogen;        -   R′ is H, C₁-C₄ alkyl, benzyl, C₁-C₆ alkanoyl,            phenyl(C₁-C₄)alkanoyl, pyridyl(C₁-C₄)alkyl, —SO₂-alkyl,            —SO₂-phenyl, —SO₂-pyridyl, pyridyl(C₁-C₆)alkanoyl, wherein            the alkyl portion of the alkyl and alkanoyl groups are            optionally substituted with halogen or C₁-C₄ alkoxy,            -   wherein the phenyl and pyridyl groups are optionally                substituted with C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,                CF₃, OCF₃;        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 17LL. Compounds according to Embodiment 17KK, wherein

-   -   R₃ is H, halogen, methyl, methoxy, CF₃, or CN;    -   R₄ is halogen, methyl, methoxy, CF₃, OCF₃, CN, —NHR′, or —NR′R″;    -   R_(3′) is H, or halogen;        -   R′ is H, or C₁-C₄ alkyl; and        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 17MM. Compounds according to Embodiment 17LL wherein R₃ is H,or halogen; R₄ is halogen, methyl, CF₃, or methoxy; and R_(3′) is H, orhalogen.

Embodiment 17NN. Compounds according to Embodiment 17MM wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl), methyl, or CF₃;and R_(3′) is H. In another aspect, R₄ is methyl. In still anotheraspect, R₄ is CF₃. In yet another aspect, R₄ is Cl.

Embodiment 18. Compounds according to any one of Embodiments 17A, 17B,17C, 17C1, 17C2, 17C3, 17C4, 17D, 17E, 17E1, 17E2, 17E3, 17E4, 17F, 17G,17H, 17H1, 17H2, 17H3, 17H4, 17I, 17J, 17K, 17L, 17M, 17N, 17O, 17P,17Q, 17Q1, 17Q2, 17Q3, 17Q4, 17R, 17S, 17T, 17U, 17V, 17W, 17X, 17Y,17Y1, 17Y2, 17Y3, 17Y4, 17Z, 17Z1, 17Z2, 17Z3, 17Z4, 17AA, 17BB, 17CC,17CC1, 17CC2, 17CC3, 17CC4, 17DD, 17EE, 17FF, 17GG, 17HH, 17II, 17JJ,17KK, 17LL, 17MM, or 17NN, wherein R₁ is C₃-C₈ cycloalkyl optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄hydroxyalkyl, or OH.

Embodiment 18A. Compounds according to Embodiment 18, wherein the C₃-C₈cycloalkyl group is substituted with one or two methyl groups. In stillanother aspect, the C₃-C₈ cycloalkyl group is substituted with only—CH₂—OH. In yet still another aspect, the C₃-C₈ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH.

Embodiment 18B. Compounds according to Embodiment 18, wherein thecycloalkyl group is a C₃-C₆ cycloalkyl group. In another aspect, thecycloalkyl group is substituted with one or two methyl groups. In stillanother aspect, the C₃-C₆ cycloalkyl group is substituted with only—CH₂—OH. In yet still another aspect, the C₃-C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH. In another aspect,the cycloalkyl group is substituted with at least one OH group. In stillanother aspect, the cycloalkyl group is substituted with only one OHgroup. In still another aspect, the cycloalkyl group is a cyclopropylgroup.

Embodiment 18C. Compounds according to Embodiment 18, wherein thecycloalkyl group is a C₅-C₆ cycloalkyl. In another aspect, the C₅-C₆cycloalkyl group is substituted with one or two methyl groups. In oneaspect, the cycloalkyl group is substituted with one methyl group. Inanother aspect, the cycloalkyl group is substituted with two methylgroups. In still another aspect, the C₅-C₆ cycloalkyl group issubstituted with only —CH₂—OH. In yet still another aspect, the C₅-C₆cycloalkyl group is substituted with one methyl group and one —CH₂—OH orone OH group. In another aspect, the cycloalkyl group is substitutedwith at least one OH group. In still another aspect, the cycloalkylgroup is substituted with only one OH group. In one aspect, the methylgroup and (the —CH₂—OH group or the OH group) are in a 1, 2 relationshiprelative to each other. In another aspect, the methyl group and (the—CH₂—OH group or the OH group) are in a 1, 3 relationship relative toeach other. In still another aspect, the methyl group and (the —CH₂—OHgroup or the OH group) are in a 1,4 relationship relative to each other.

Embodiment 18D. Compounds according to Embodiment 18, wherein thecycloalkyl group is a C₆ cycloalkyl. In another aspect, the C₆cycloalkyl group is substituted with one or two methyl groups. In oneaspect, the cycloalkyl group is substituted with one methyl group. Instill another aspect, the C₆ cycloalkyl group is substituted with only—CH₂—OH. In yet still another aspect, the C₆ cycloalkyl group issubstituted with one methyl group and one —CH₂—OH. In another aspect,the cycloalkyl group is substituted with at least one OH group. In oneaspect, the methyl group and (the —CH₂—OH group or the OH group) are ina 1, 2 relationship relative to each other. In another aspect, themethyl group and (the —CH₂—OH group or the OH group) are in a 1, 3relationship relative to each other. In still another aspect, the methylgroup and (the —CH₂—OH group or the OH group) are in a 1,4 relationshiprelative to each other.

Embodiment 18E. Compounds according to Embodiment 18D, wherein

-   -   R₁ is

Embodiment 18E1. Compounds according to embodiment 18E, wherein

-   -   R₁ is

Embodiment 18F. Compounds according to Embodiment 18, wherein thecycloalkyl group is a C₇-C₈ cycloalkyl.

Embodiment 19. Compounds according to any one of Embodiments 17A, 17B,17C, 17C1, 17C2, 17C3, 17C4, 17D, 17E, 17E1, 17E2, 17E3, 17E4, 17F, 17G,17H, 17H1, 17H2, 17H3, 17H4, 17I, 17J, 17K, 17L, 17M, 17N, 170, 17P,17Q, 17Q1, 17Q2, 17Q3, 17Q4, 17R, 17S, 17T, 17U, 17V, 17W, 17X, 17Y,17Y1, 17Y2, 17Y3, 17Y4, 17Z, 17Z1, 17Z2, 17Z3, 17Z4, 17Z5, 17AA, 17BB,17CC, 17CC1, 17CC2, 17CC3, 17CC4, 17DD, 17EE, 17FF, 17GG, 17HH, 17II,17JJ, 17KK, 17LL, 17MM, or 17NN, wherein R₁ is heterocycloalkyl orheterocycloalkyl(C₁-C₄)alkyl wherein the heterocycloalkyl group ispiperidinyl, pyrrolidinyl, tetrahydrofuranyl, pyrazolyl, or morpholinyl,wherein the heterocycloalkyl groups are optionally substituted with 1 or2 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl,phenyl(C₁-C₄)alkyl, OH, halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or C₁-C₄alkoxycarbonyl.

Embodiment 19A. Compounds according to Embodiment 19, wherein R₁ isheterocycloalkyl, which is piperidin-3-yl, piperidin-4-yl,pyrrolidin-2-yl, tetrahydrofuranyl, pyrazolyl, or morpholinyl, whereinthe heterocycloalkyl groups are optionally substituted with 1 or 2groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl,phenyl(C₁-C₄)alkyl, OH, halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or C₁-C₄alkoxycarbonyl.

Embodiment 19B. Compounds according to Embodiment 19, wherein R₁ isheterocycloalkyl, which is piperidin-3-yl, piperidin-4-yl, pyrrolidinyl,pyrazolyl, or morpholinyl, wherein the heterocycloalkyl groups areoptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl, C₁-C₄ alkoxy, phenyl, phenyl(C₁-C₄)alkyl, OH, halogen, CO₂H,C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or C₁-C₄ alkoxycarbonyl.

Embodiment 19C. Compounds according to Embodiment 19, wherein theheterocycloalkyl groups are optionally substituted with 1 or 2 groupsthat are independently methyl, methoxy, phenyl, benzyl, OH, halogen,CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or tert-butylcarbonyl. In anotherembodiment, the heterocycloalkyl group is substituted with methyl.

Embodiment 19D. Compounds according to Embodiment 19, wherein R₁ istetrahydrofuranyl, which is optionally substituted with a methyl group.

Embodiment 19E. Compounds according to Embodiment 19, wherein

-   -   R₁ is heterocycloalkyl(C₁-C₄)alkyl, which is piperidinyl,        pyrrolidinyl, tetrahydrofuranyl, pyrazolyl, or morpholinyl,        wherein the heterocycloalkyl groups are optionally substituted        with 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄        alkoxy, phenyl, phenyl(C₁-C₄)alkyl, halogen, CO₂H, C₁-C₄        alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or C₁-C₄ alkoxycarbonyl.

Embodiment 19F. Compounds according to Embodiment 19, wherein

-   -   R₁ is heterocycloalkyl(C₁-C₄)alkyl, which is piperidinyl,        pyrrolidinyl, pyrazolyl, or morpholinyl, wherein the        heterocycloalkyl groups are optionally substituted with 1 or 2        groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl,        phenyl(C₁-C₄)alkyl, halogen, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl,        or C₁-C₄ alkoxycarbonyl.

Embodiment 19G. Compounds according to Embodiment 19, wherein theheterocycloalkyl groups are optionally substituted with 1 or 2 groupsthat are independently methyl, methoxy, phenyl, benzyl, halogen, CO₂H,C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or tert -butylcarbonyl.

Embodiment 19H. Compounds according to Embodiment 19, wherein R₁ istetrahydrofuranyl(C₁-C₄)alkyl, which is optionally substituted with amethyl group.

Embodiment 19I. Compounds according to any one of Embodiments 19, 19B,19D, 19E, 19F, or 19H, wherein the heterocycloalkyl groups areunsubstituted.

Embodiment 19J. Compounds according to any one of Embodiments 19, 19E,19F, 19G, 19H, or 19I, wherein the alkyl group is a C₁-C₂ alkyl group.In another aspect, the alkyl group is a C₁ alkyl group.

Embodiment 20. Compounds according to any one of Embodiments 17A, 17B,17C, 17C1, 17C2, 17C3, 17C4, 17D, 17E, 17E1, 17E2, 17E3, 17E4, 17F, 17G,17H, 17H1, 17H2, 17H3, 17H4, 17I, 17J, 17K, 17L, 17M, 17N, 17O, 17P,17Q, 17Q1, 17Q2, 17Q3, 17Q4, 17R, 17S, 17T, 17U, 17V, 17W, 17X, 17Y,17Y1, 17Y2, 17Y3, 17Y4, 17Z, 17Z1, 17Z2, 17Z3, 17Z4, 17AA, 17BB, 17CC,17CC1, 17CC2, 17CC3, 17CC4, 17DD, 17EE, 17FF, 17GG, 17HH, 17II 17JJ,17KK, 17LL, 17MM, or 17NN, wherein R₁ is heteroaryl(C₁-C₄)alkyl, whereinthe heteroaryl group is pyridyl, pyrimidyl, furanyl, or thienyl and theheteroaryl group is optionally substituted with 1, 2, or 3 groups thatare independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkyl,C₁-C₄ alkoxy or OH.

Embodiment 20A. Compounds according to Embodiment 20, wherein R₁ isheteroaryl(C₁-C₄)alkyl, wherein the heteroaryl group is pyridyl, orpyrimidyl, each of which is optionally substituted with 1, or 2 groupsthat are independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, C₁-C₄ alkyl,C₁-C₄ alkoxy or OH.

Embodiment 20B. Compounds according to Embodiment 20A, wherein theheteroaryl group is substituted with 1, or 2 groups that areindependently halogen, methyl, methoxy, or OH.

Embodiment 20C. Compounds according to Embodiment 20A, wherein R₁ isheteroaryl(C₁-C₄)alkyl, wherein the heteroaryl group is furanyl, orthienyl each is optionally substituted with 1, 2, or 3 groups that areindependently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy or OH.

Embodiment 20D. Compounds according to any one of Embodiments 20, 20A,20B, or 20C, wherein the alkyl group is a C₁-C₂ alkyl group. In anotheraspect, the alkyl group is a C₁ alkyl group.

Embodiment 20E. Compounds according to any one of Embodiments 20, 20A,20B, 20C, or 20D, wherein the heteroaryl group is un-substituted.

Embodiment 21. In another aspect, the invention provides compounds ofFormula X

or pharmaceutically acceptable salts thereof, wherein

-   -   L is C₁-C₆ alkylene or C₂-C₆ alkenylene;    -   R₁ is C₂-C₆ alkynyl, C₂-C₆ alkenyl, or C₁-C₈ alkyl wherein each        is optionally substituted with 1, 2, or 3 groups that are        independently C₁-C₆ alkoxy, OH, halogen, CN, C₁-C₆ thioalkoxy,        phenyl, naphthyl, pyridyl, pyrimidyl, furanyl, thienyl, C₃-C₈        cycloalkyl, NH₂, NH(C₁-C₆) alkyl, N(C₁-C₆)alkyl(C₁-C₆ alkyl),        —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆)alkyl,        —C(O)phenyl, or C₁-C₆ alkoxycarbonyl,        -   wherein each of the cyclic groups is optionally substituted            with 1, 2, 3, or 4 groups that are independently halogen,            C₁-C₄ alkyl, C₁-C₄ alkoxy, NH₂, NH(C₁-C₆) alkyl, N(C₁-C₆)            alkyl (C₁-C₆ alkyl), —SO₂—(C₁-C₆)alkyl, or OH; or    -   R₁ is C₃-C₈ cycloalkyl optionally substituted with 1 or 2 groups        that are independently C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, or OH;        or    -   R₁ is heterocycloalkyl or heterocycloalkyl(C₁-C₄)alkyl wherein        the heterocycloalkyl group is piperidinyl, pyrrolidinyl,        tetrahydrofuranyl, pyrazolyl, or morpholinyl, wherein the        heterocycloalkyl groups are optionally substituted with C₁-C₄        alkyl, C₁-C₄ alkoxy, phenyl, phenyl(C₁-C₄)alkyl, halogen or        C₁-C₄ alkoxycarbonyl; or    -   R₁ is heteroaryl(C₁-C₄)alkyl, wherein the heteroaryl group is        pyridyl, pyrimidyl, furanyl, or thienyl and the heteroaryl group        is optionally substituted with 1, 2, or 3 groups that are        independently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy or OH;    -   R₃ is H, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkyl,        CN,    -   R₄ is H, halogen, C₁-C₄ alkyl optionally substituted with        —CO₂—(C₁-C₆ alkyl), C₁-C₆ alkoxy, C₁-C₆ haloalkyl, C₁-C₆        haloalkoxy, CN, aryloxy, isocyanato, —SO₂—(C₁-C₆ alkyl), —NHR′,        —NR′R″, C₁-C₆ alkanoyl, pyridyl, phenyl, or    -   R₃ and R₄ and the carbons to which they are attached form a        heterocycloalkyl ring which is optionally substituted with 1, 2,        or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,        halogen, or C₁-C₄ alkanoyl wherein the alkanoyl group is        optionally substituted with up to 3 halogen atoms;    -   R_(3′) is H, —SO₂—NR′R″, halogen, or    -   R₄ and R_(3′) and the carbons to which they are attached form a        phenyl ring; or    -   R₄ and R_(3′) and the carbons to which they are attached form a        1-oxa-2,3-diazacyclopentyl ring;    -   R₅ is H, halogen, C₁-C₆ alkoxy, CF₃, CO₂H, C₁-C₄ alkoxycarbonyl,        —O—(C₁-C₄ alkyl)-CO₂—(C₁-C₄ alkyl), —C(O)NH₂, —C(O)NH(C₁-C₄)        alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl, morpholinyl, oxazolyl,        pyrazolyl, thiomorpholinyl, thiomorpholinyl S,S-dioxide,        piperidinyl, pyrrolidinyl, halogen, C₁-C₆ alkyl, phenyl        optionally substituted with 1, 2, 3, 4 or 5 groups that are        independently halogen, C₁-C₆ alkyl, or C₁-C₄ alkoxy, CN, or        —(C₁-C₄ alkyl)-SO₂-phenyl,    -   R₆ is H, C₁-C₆ alkoxy, halogen, C₁-C₆ alkyl, CF₃, OCF₃,        phenyl(C₁-C₄)alkoxy, phenyloxy, CO₂H, C₁-C₆ alkoxycarbonyl,        —C(O) NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆)        alkyl, CN, C₂-C₆ alkenyl, or C₁-C₆ alkyl, wherein the above        phenyl groups are optionally substituted with 1, 2, 3, 4 or 5        groups that are independently halogen, C₁-C₆ alkyl, CO₂H, C₁-C₄        alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or C₁-C₄ alkoxy, or    -   R₅, R₆, and the carbons to which they are attached form a phenyl        ring, which is optionally substituted with 1 or 2 groups that        are independently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, or        OCF₃;    -   R₇ is H, OH, C₁-C₆ alkoxy, —O—SO₂-phenyl where the phenyl is        optionally substituted with halogen, halogen, C₁-C₆ alkyl,        phenyloxy, benzyloxy, CF₃, CO₂H, OH, —O—C(O)—(C₁-C₄ alkyl),        C₁-C₆ alkoxycarbonyl, —C(O)NR₃₀R₃₁, —NHR′, —NR′R″,        —N(R₁₆)C(O)—R₁₇, thiazolyl, thiazolyl(C₁-C₆)alkoxy,        pyridyl(C₁-C₆)alkoxy, oxazolyl(C₁-C₄)alkoxy,        pyrazolyl(C₁-C₄)alkoxy, wherein the thiazolyl, pyridyl,        oxazolyl, and pyrazolyl groups are optionally substituted with        1, 2, or 3 groups that are independently C₁-C₆ alkyl, C₁-C₆        alkoxy, or halogen, phenyl optionally substituted with 1, 2, 3,        4 or 5 groups that are independently halogen, C₁-C₆ alkyl, C₁-C₄        alkoxy, OCF₃, CN, or C₁-C₆ thioalkoxy, —S(O)_(x)—R₂₅, or —(C₁-C₄        alkyl)-S(O)_(x)—R₂₅; wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;        -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄            alkyl), phenyl, or pyridyl; or        -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl;        -   R₃₀ and R₃₁ are independently H, C₁-C₆ alkyl, phenyl,            benzyl, pyridyl, imidazolyl, thiazolyl, oxazolyl, or            indolyl, or        -   R₃₀, R₃₁, and the nitrogen to which they are attached form a            heterocycloalkyl ring containing from 3 to 7 ring members;        -   R₁₆ is H or C₁-C₆ alkyl;        -   R₁₇ is C₁-C₆ alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl,            pyrazinyl, thienyl, C₁-C₆ alkoxy, OH, phenyloxy, pyridyloxy,            pyrimidyloxy, pyridazyloxy, pyrazinyloxy, thienyloxy,            phenyl(C₁-C₄)alkoxy, or —NR₁₈R₁₉;        -   R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl,            pyridyl, thienyl, piperidinyl, pyrrolidinyl, morpholinyl,            thiomorpholinyl, thiomorpholinyl 1,1-dioxide,            tetrahydro-thiopyranyl 1,1-dioxide, or phenyl(C₁-C₄) alkyl;            or    -   R₆, R₇, and the carbons to which they are attached form a phenyl        ring, which is optionally substituted with 1 or 2 groups that        are independently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, or        OCF₃; or    -   R₆ and R₇ are —O—CH₂CH₂—O—, or —O—CH₂—O—;    -   R₈ is H, halogen, C₁-C₆ alkoxy, C₁-C₆ alkyl, cyano, —O-phenyl        wherein the phenyl group is optionally substituted with halogen,        C₂-C₄ alkenyl, C₁-C₄ alkoxycarbonyl, benzyloxy, —S(O)_(x)—R₂₅,        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or CO₂H, or    -   R₇ and R₈ are —O—CH₂CH₂—O—, or —O—CH₂—O—;    -   R₉ is H, halogen, C₁-C₆ alkyl optionally substituted with        —SO2-phenyl, cyano, C₁-C₆ alkoxy, or phenyl;        -   R′ is H, C₁-C₆ alkyl, or C₁-C₆ alkanoyl, wherein the alkyl            portion of the alkyl and alkanoyl groups are optionally            substituted with halogen,        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 21A. Compounds according to Embodiment 21, wherein R₅, R₆,R₇, R₈, and R₉ are independently hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄alkoxy, NH₂, NH(C₁-C₆)alkyl, N(C₁-C₆)alkyl(C₁-C₆ alkyl),—SO₂—(C₁-C₆)alkyl, or OH.

Embodiment 21B. Compounds according to either Embodiment 21 orEmbodiment 21A wherein

-   -   R₁ is        wherein    -   R₂₁ and R₂₂ are independently H or C₁-C₆ alkyl;    -   R₂₃ is H, —C(O)NR₃₀R₃₁, C₁-C₆ alkyl, CO₂H, halogen, C₁-C₆        alkoxycarbonyl, phenyl, naphthyl, benzyl, pyridyl, pyrimidyl,        furanyl, or thienyl;        -   R₃₀ and R₃₁ are independently H, C₁-C₆ alkyl, phenyl,            benzyl, pyridyl, thiazolyl, oxazolyl, or indolyl, or        -   R₃₀, R₃₁, and the nitrogen to which they are attached form a            azepanyl, piperidinyl, pyrrolidinyl, morpholinyl,            thiomorpholinyl, or thiomorpholinyl 1,1-dioxide.

Embodiment 21B1. Compounds according to Embodiment 21B, wherein R₂₃ isH, or —C(O)NR₃₀R₃₁, and R₃₀ and R₃₁ are independently H, C₁-C₆ alkyl,phenyl, or benzyl.

Embodiment 21B2. Compounds according to Embodiment 21B, wherein R₂₃ isH, or —C(O)NR₃₀R₃₁, and R₃₀ and R₃₁ are independently H, methyl,pyridyl, thiazolyl, oxazolyl, or indolyl.

Embodiment 21B2. Compounds according to Embodiment 21B, wherein R₂₃ isH, or —C(O)NR₃₀R₃₁, and R₃₀, R₃₁, and the nitrogen to which they areattached form a azepanyl, piperidinyl, pyrrolidinyl, morpholinyl,thiomorpholinyl, or thiomorpholinyl 1,1-dioxide.

Embodiment 21B3. Compounds according to any one of Embodiments 21B,21B1, or 21B2, wherein R₂₃ is H, C₁-C₆ alkyl, CO₂H, or C₁-C₆alkoxycarbonyl.

Embodiment 21B4. Compounds according to any one of Embodiments 21B,21B1, or 21B2, wherein R₂₃ is H, phenyl, naphthyl, benzyl, pyridyl,pyrimidyl, furanyl, or thienyl.

Embodiment 21C. Compounds according to either Embodiment 21 orEmbodiment 21A wherein

-   -   R₁ is        wherein    -   m is 0, 1, 2, or 3;    -   R₂₀ is H or methyl; and    -   cycloalkyl is C₃-C₇ cycloalkyl wherein the cyclic portion is        optionally substituted with 1, 2, 3, 4, or 5 groups that are        independently halogen, C₁-C₆ alkyl, OH, or C₁-C₆ alkoxy.

Embodiment 21D. Compounds according to Embodiment 21, wherein cycloalkylis cyclopropyl, cyclopentyl, or cyclohexyl, wherein the cyclic portionis optionally substituted with 1, or 2 groups that are independentlyhalogen, C₁-C₄ alkyl, OH, or C₁-C₄ alkoxy.

Embodiment 21E. Compounds according to either Embodiment 21 orEmbodiment 21A wherein

-   -   R₁ is of the formula:        wherein    -   m is 0, 1, 2, or 3;    -   R₂₀ is H or methyl; and    -   heterocycloalkyl is 4-oxo-4H-chromen-3-yl, 2H-chromen-3-yl,        pyrrolidinonyl dione, isoindol-2-yl dione, 1,3-dioxolan-2-yl,        dioxanyl, or tetrahydropyran-2-yl, wherein the cyclic portion of        each is optionally substituted with 1, 2, 3, 4, or 5 groups that        are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, or halogen.

Embodiment 21F. Compounds according to Embodiment 21E, wherein m is 0or 1. In another aspect, m is 0 or 1 and heterocycloalkyl isisoindol-2-yl dione, 4-oxo-4H-chromen-3-yl, or 2H-chromen-3-yl.

Embodiment 21G. Compounds according to Embodiment 21E, wherein m is 1 or2. In another aspect, m is 1 or 2 and heterocycloalkyl is isoindol-2-yldione, 4-oxo-4H-chromen-3-yl, or 2H-chromen-3-yl.

Embodiment 21H. Compounds according to any one of Embodiments 21, 21A,21B, 21C, 21D, 21E, 21F, or 21G, wherein

-   -   R₅ is H, C₁-C₆ alkoxy, CF₃, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl,        morpholinyl, oxazolyl, pyrazolyl, thiomorpholinyl,        thiomorpholinyl S,S-dioxide, piperidinyl, pyrrolidinyl, halogen,        C₁-C₆ alkyl, phenyl optionally substituted with 1, 2, 3, 4 or 5        groups that are independently halogen, C₁-C₆ alkyl, or C₁-C₄        alkoxy, CN, —(C₁-C₄ alkyl)-SO₂-phenyl,    -   R₆ is H, C₁-C₆ alkoxy, halogen, C₁-C₆ alkyl, CF₃, OCF₃,        phenyl(C₁-C₄)alkoxy, phenyloxy, CO₂H, C₁-C₆ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl,        CN, C₂-C₆ alkenyl, wherein the above phenyl groups are        optionally substituted with 1, 2, 3, 4 or 5 groups that are        independently halogen, C₁-C₆ alkyl, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl,        or C₁-C₄ alkoxy;    -   R₇ is H, OH, C₁-C₆ alkoxy, —O—SO₂-phenyl, halogen, C₁-C₆ alkyl,        phenyloxy, CF₃, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NR₃₀R₃₁, —NHR′,        —NR′R″, —N(R₁₆)C(O)—R₁₇, thiazolyl(C₁-C₆)alkoxy,        pyridyl(C₁-C₆)alkoxy, oxazolyl(C₁-C₄)alkoxy,        pyrazolyl(C₁-C₄)alkoxy, wherein the thiazolyl, pyridyl,        oxazolyl, and pyrazolyl groups are optionally substituted with        1, 2, or 3 groups that are independently C₁-C₆ alkyl, C₁-C₆        alkoxy, or halogen, phenyl optionally substituted with 1, 2, 3,        4 or 5 groups that are independently halogen, C₁-C₆ alkyl, C₁-C₄        alkoxy, OCF₃, CN, CO₂H, C₁-C₆ alkoxycarbonyl, C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl,        —S(O)_(x)—R₂₅, or —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅ or C₁-C₆        thioalkoxy, wherein        -   R₃₀ and R₃₁ are independently H, C₁-C₆ alkyl, phenyl,            benzyl, pyridyl, imidazolyl, thiazolyl, oxazolyl, or            indolyl, or        -   R₃₀, R₃₁, and the nitrogen to which they are attached form a            heterocycloalkyl ring containing from 3 to 7 ring members;        -   R₁₆ is H or C₁-C₆ alkyl;        -   R₁₇ is C₁-C₆ alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl,            pyrazinyl, thienyl, C₁-C₆ alkoxy, OH, phenyloxy, pyridyloxy,            pyrimidyloxy, pyridazyloxy, pyrazinyloxy, thienyloxy,            phenyl(C₁-C₄)alkoxy, or —NR₁₈R₁₉;    -   R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl, pyridyl,        thienyl, piperidinyl, pyrrolidinyl, morpholinyl,        thiomorpholinyl, thiomorpholinyl 1,1-dioxide, tetrahydro        -thiopyranyl 1,1-dioxide, or phenyl(C₁-C₄) alkyl;    -   R₈ is H, halogen, C₁-C₆ alkoxy, C₁-C₆ alkyl, —S(O)_(x)—R₂₅,        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅ or CO₂H;    -   R₉ is H, halogen, C₁-C₆ alkoxy, C₁-C₆ alkyl,        -   R′ is H, C₁-C₆ alkyl, or C₁-C₆ alkanoyl, wherein the alkyl            portion of the alkyl and alkanoyl groups are optionally            substituted with halogen,        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 21I. Compounds according to Embodiment 21H, wherein

-   -   R₅ is H, C₁-C₄ alkoxy, CF₃, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or        —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl;    -   R₆ is H, C₁-C₄ alkoxy, halogen, C₁-C₄ alkyl, CF₃, OCF₃, CO₂H,        C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, CN, or C₂-C₆ alkenyl;    -   R₈ is H, halogen, C₁-C₄ alkoxy, C₁-C₄ alkyl, or CO₂H; and    -   R₉ is H, halogen, C₁-C₄ alkoxy, or C₁-C₄ alkyl.

Embodiment 21J. Compounds according to Embodiment 21I, wherein R₃ is H,halogen, methyl, methoxy, CF₃, or CN; R₄ is halogen, methoxy, methyl,CF₃, OCF₃, or CN; R_(3′) is H, or halogen.

Embodiment 21K. Compounds according to Embodiment 21J, wherein R₇ is H,OH, C₁-C₄ alkoxy, halogen, C₁-C₄ alkyl, CF₃, CO₂H, C₁-C₆ alkoxycarbonyl,—C(O)NR₃₀R₃₁, thiazolyl(C₁-C₆)alkoxy, pyridyl(C₁-C₆)alkoxy,oxazolyl(C₁-C₄)alkoxy, pyrazolyl(C₁-C₄)alkoxy, wherein the thiazolyl,pyridyl, oxazolyl, and pyrazolyl groups are optionally substituted with1, 2, or 3 groups that are independently C₁-C₆ alkyl, C₁-C₆ alkoxy, orhalogen, or phenyl optionally substituted with 1, 2, 3, 4 or 5 groupsthat are independently halogen, C₁-C₆ alkyl, C₁-C₄ alkoxy, OCF₃, CO₂H,C₁-C₆ alkoxycarbonyl, CN, or C₁-C₆ thioalkoxy; and

-   -   R₃₀ and R₃₁ are independently H, C₁-C₆ alkyl, phenyl, or benzyl.

Embodiment 21K1. Compounds according to Embodiment 21J, wherein R₇ is—S(O)_(x)—R₂₅, or —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅

-   -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 21K2. Compounds according to Embodiment 21K1, wherein R₂₅ isC₁-C₆ alkyl or OH.

Embodiment 21K3. Compounds according to Embodiment 21K1, wherein R₂₅ isC₁-C₄ alkyl or NR₂₆R₂₇; and R₂₆ and R₂₇ are independently H, C₁-C₆alkyl, phenyl (C₁-C₄ alkyl) , phenyl, or pyridyl.

Embodiment 21K4. Compounds according to Embodiment 21K1, wherein R₂₅ isC₁-C₄ alkyl or NR₂₆R₂₇; and R₂₆, R₂₇ and the nitrogen to which they areattached represent pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl,or imidazolidinyl.

Embodiment 21L. Compounds according to Embodiment 21K, wherein R₇ is H,OH, C₁-C₄ alkoxy, halogen, C₁-C₄ alkyl, CF₃, CO₂H, —C(O) NR₃₀R₃₁, orC₁-C₄ alkoxycarbonyl; and R₃₀ and R₃₁ are independently H or C₁-C₆alkyl.

Embodiment 21M. Compounds according to Embodiment 21L, wherein R₇ is H,OH, methoxy, halogen, methyl, CF₃, CO₂H, —C(O)NR₃₀R₃₁, or C₁-C₂alkoxycarbonyl; and R₃₀ and R₃₁ are independently H or C₁-C₄ alkyl.

Embodiment 21N. Compounds according to Embodiment 21M, wherein R₇ isCO₂H, —C(O)NR₃₀R₃₁, or C₁-C₂ alkoxycarbonyl.

Embodiment 21O. Compounds according to Embodiment 21M, wherein R₇ is OH,methoxy, halogen, methyl, or CF₃.

Embodiment 21P. Compounds according to any one of Embodiments 21K, 21K1,21K2, 21K3, 21K4, 21L, 21M, 21N or 21O, wherein R₃ is H, or halogen;

-   -   R₄ is halogen, methyl, CF₃, or methoxy; and R_(3′) is H or        halogen.

Embodiment 21Q. Compounds according to Embodiment 21P, wherein R₅ is H,methoxy, CF₃, CO₂H, C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl,or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl;

-   -   R₆ is H, C₁-C₂ alkoxy, halogen, C₁-C₂ alkyl, CF₃, OCF₃, CO₂H,        C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or        —C(O)N(C₁-C₄) alkyl (C₁-C₄) alkyl;    -   R₈ is H or halogen (preferred halogens are F or Cl); and    -   R₉ is H or halogen (preferred halogens are F or Cl).

Embodiment 21R. Compounds according to Embodiment 21Q wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl); and R_(3′) is H.In another aspect, R₄ is methyl. In still another aspect, R₄ is CF₃. Inyet another aspect, R₄ is Cl.

Embodiment 21S. Compounds according to Embodiment 21R, wherein R₅ is H,methoxy, CF₃, CO₂H, or C₁-C₂ alkoxycarbonyl; R₆ is H, methoxy, halogen,methyl, CF₃, OCF₃, CO₂H, or C₁-C₂ alkoxycarbonyl (in one aspect, C₂alkoxycarbonyl); R₈ is H, F or Cl; and R₉ is H, F or Cl.

Embodiment 21T. Compounds according to Embodiment 21J, wherein R₇ is H,—NHR′, —NR′R″ or —N(R₁₆) C(O)—R₁₇; R₁₆ is H or C₁-C₄ alkyl; R₁₇ is C₁-C₆alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, thienyl, C₁-C₆alkoxy, phenyloxy, pyridyloxy, pyrimidyloxy, pyridazyloxy, pyrazinyloxy,thienyloxy, phenyl(C₁-C₄)alkoxy, or —NR₁₈R₁₉; and R₁₈ and R₁₉ areindependently H, C₁-C₆ alkyl, phenyl, pyridyl, thienyl, piperidinyl,pyrrolidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl 1,1-dioxide,tetrahydro-thiopyranyl 1,1-dioxide, or phenyl(C₁-C₄) alkyl; wherein R′is H, C₁-C₄ alkyl, or C₁-C₄ alkanoyl; R″ is C₁-C₄ alkyl, wherein thealkyl group is optionally substituted with halogen.

Embodiment 21U. Compounds according to Embodiment 21T, wherein R₃ is H,or halogen; R₄ is halogen, methyl, CF₃, or methoxy; and R_(3′) is H orhalogen. In another aspect, R₄ is methyl. In still another aspect, R₄ isCF₃. In yet another aspect, R₄ is Cl.

Embodiment 21V. Compounds according to Embodiment 21U, wherein R₅ is H,methoxy, CF₃, CO₂H, C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl,or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl;

-   -   R₆ is H, C₁-C₂ alkoxy, halogen, C₁-C₂ alkyl, CF₃, OCF₃, CO₂H,        C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or        —C(O)N(C₁-C₄)alkyl (C₁-C₄)alkyl;    -   R₈ is H or halogen (preferred halogens are F or Cl); and    -   R₉ is H or halogen (preferred halogens are F or Cl).

Embodiment 21W. Compounds according to Embodiment 21V wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl), methyl, or CF₃;and R_(3′) is H.

Embodiment 21X. Compounds according to Embodiment 21W, wherein R₅ is H,methoxy, CF₃, CO₂H, or C₁-C₂ alkoxycarbonyl;

-   -   R₆ is H, methoxy, halogen, methyl, CF₃, OCF₃, CO₂H, or C₁-C₂        alkoxycarbonyl (in one aspect, C₂ alkoxycarbonyl);    -   R₈ is H, F or Cl; and    -   R₉ is H, F or Cl.

Embodiment 21Y. Compounds according to any one of Embodiments 21U, 21V,21W, or 21X, wherein R₇ is H or —N(R₁₆)C(O)—R₁₇; wherein R₁₆ is H orC₁-C₄ alkyl; R₁₇ is C₁-C₆ alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl,pyrazinyl, thienyl, C₁-C₆ alkoxy, phenyloxy, pyridyloxy, pyrimidyloxy,pyridazyloxy, pyrazinyloxy, thienyloxy, phenyl(C₁-C₄)alkoxy, or—NR₁₈R₁₉; and R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl,pyridyl, thienyl, piperidinyl, pyrrolidinyl, morpholinyl,thiomorpholinyl, thiomorpholinyl 1,1-dioxide, tetrahydro-thiopyranyl1,1-dioxide, or phenyl(C₁-C₄) alkyl.

Embodiment 21Z. Compounds according to Embodiment 21Y, wherein R₁₇ isC₁-C₄ alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, thienyl,C₁-C₄ alkoxy, phenyloxy, pyridyloxy, pyrimidyloxy, pyridazyloxy,pyrazinyloxy, thienyloxy, phenyl (C₁-C₄) alkoxy.

Embodiment 21AA. Compounds according to Embodiment 21Z, wherein R₁₇ isC₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl, phenyloxy, or phenyl(C₁-C₂)alkoxy.

Embodiment 21BB. Compounds according to Embodiment 21Z, wherein R₁₇ ispyridyl, pyrimidyl, pyridazyl, pyrazinyl, thienyl, pyridyloxy,pyrimidyloxy, pyridazyloxy, pyrazinyloxy, or thienyloxy.

Embodiment 21BB. Compounds according to Embodiment 21Z, wherein R₁₇ is—NR₁₈R₁₉; and R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl,pyridyl, thienyl, piperidinyl, pyrrolidinyl, morpholinyl,thiomorpholinyl, thiomorpholinyl 1,1-dioxide, tetrahydro-thiopyranyl1,1-dioxide, or phenyl(C₁-C₄) alkyl.

Embodiment 21CC. Compounds according to Embodiment 21Y, wherein R₁₇ is—NR₁₈R₁₉; and R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl,pyridyl, thienyl, piperidinyl, pyrrolidinyl, morpholinyl, orphenyl(C₁-C₄) alkyl.

Embodiment 21DD. Compounds according to Embodiment 21CC, wherein R₁₈ andR₁₉ are independently H, C₁-C₄ alkyl, phenyl, or phenyl(C₁-C₂) alkyl.

Embodiment 21EE. Compounds according to Embodiment 21CC, wherein R₁₈ andR₁₉ are independently H, pyridyl, thienyl, piperidinyl, pyrrolidinyl,morpholinyl, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, ortetrahydro-thiopyranyl 1,1-dioxide. In another aspect, one of R₁₈ andR₁₉ is H.

Embodiment 21EE1. Compounds according to Embodiment 21CC, wherein R₁₈and R₁₉ are independently H, pyridyl, piperidinyl, pyrrolidinyl, ormorpholinyl. In another aspect, one of R₁₈ and R₁₉ is H. In anotheraspect, only one of R₁₈ and R₁₉ is H.

Embodiment 21EE2. Compounds according to Embodiment 21CC, wherein R₁₈and R₁₉ are independently H, thienyl, thiomorpholinyl, thiomorpholinyl1,1-dioxide, or tetrahydro -thiopyranyl 1,1-dioxide. In another aspect,one of R₁₈ and R₁₉ is H. In another aspect, only one of R₁₈ and R₁₉ isH.

Embodiment 21FF. Compounds according to any one of Embodiments 21U, 21V,21W, or 21X, wherein R₇ is H, —NHR′, or —NR′R″; wherein R′ is H, C₁-C₄alkyl, or C₁-C₄ alkanoyl; R″ is C₁-C₄ alkyl, wherein the alkyl group isoptionally substituted with halogen.

Embodiment 21GG. Compounds according to Embodiment 21K, wherein R₇ isthiazolyl(C₁-C₄)alkoxy, pyridyl(C₁-C₄)alkoxy, oxazolyl(C₁-C₄)alkoxy,pyrazolyl(C₁-C₄)alkoxy, wherein the thiazolyl, pyridyl, oxazolyl, andpyrazolyl groups are optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, or halogen.

Embodiment 21HH. Compounds according to Embodiment 21GG, wherein R₇ isthiazolyl(C₁-C₂)alkoxy, pyridyl(C₁-C₂)alkoxy, oxazolyl(C₁-C₂)alkoxy, orpyrazolyl(C₁-C₂)alkoxy, wherein the thiazolyl, pyridyl, oxazolyl, andpyrazolyl groups are optionally substituted with 1, or 2 groups that areindependently methyl, methoxy, or halogen.

Embodiment 21II. Compounds according to Embodiment 21K, wherein R₇ isphenyl optionally substituted with 1, 2, 3, 4 or 5 groups that areindependently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, OCF₃, CN, CO₂H, C₁-C₄alkoxycarbonyl, C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl, or C₁-C₄ thioalkoxy. In another aspect,the phenyl is optionally substituted with 1, 2, or 3 groups, which areindependently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, OCF₃, CN, CO₂H, C₁-C₄alkoxycarbonyl, C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄) alkyl(C₁-C₄)alkyl.

Embodiment 21II1. Compounds according to Embodiment 21K, wherein R₇ isphenyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, OCF₃, CN, CO₂H, C₁-C₂alkoxycarbonyl, C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or—C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. In another aspect, the phenyl isoptionally substituted with 1 or 2 groups, which are independentlyhalogen, methyl, methoxy, CO₂H, C₁-C₂ alkoxycarbonyl, C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl.

Embodiment 21JJ. Compounds according to any one of Embodiments 21, 21A,21B, 21C, 21D, 21E, 21F, or 21G, wherein R₅, R₆, and the carbons towhich they are attached form a phenyl ring, which is optionallysubstituted with 1 or 2 groups that are independently halogen, C₁-C₄alkyl, C₁-C₄ alkoxy, CF₃, or OCF₃; and R₇, R₈, and R₉ are H.

Embodiment 21KK. Compounds according to any one of Embodiments 21, 21A,21B, 21C, 21D, 21E, 21F, or 21G, wherein R₅, R₈, and R₉ are H; and R₆,R₇, and the carbons to which they are attached form a phenyl ring, whichis optionally substituted with 1 or 2 groups that are independentlyhalogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, or OCF₃;

Embodiment 21LL. Compounds according to any one of Embodiments 21, 21A,21B, 21C, 21D, 21E, 21F, or 21G, wherein R₅, R₆, and R₉ are H; and R₇and R₈ are —O—CH₂CH₂—O—, or —O—CH₂—O—.

Embodiment 21MM. Compounds according to any one of Embodiments 21JJ,21KK, or 21LL wherein R₃ is H, halogen, methyl, methoxy, CF₃, or CN; R₄is halogen, methoxy, methyl, CF₃, OCF₃, or CN; R_(3′) is H, or halogen.

Embodiment 21NN. Compounds according to Embodiment 21MM, wherein R₃ isH, or halogen(in one aspect F or Cl); R₄ is halogen (in one aspect F orCl), methyl, CF₃, or methoxy; and R_(3′) is H or halogen (in one aspectF or Cl). In another aspect, R₄ is methyl. In still another aspect, R₄is CF₃. In yet another aspect, R₄ is Cl.

Embodiment 21OO. Compounds according to either Embodiment 21MM orEmbodiment 21NN, wherein L is a C₁-C₄ alkyl. In another aspect, L isC₁-C₂ alkyl. In yet another aspect, L is C₃-C₄ alkyl.

Embodiment 21PP. Compounds according to either Embodiment 21MM orEmbodiment 21NN, wherein L is a C₂-C₅ alkenyl. In another aspect, L isC₂-C₄ alkenyl. In yet another aspect, L is C₃-C₄ alkenyl.

Embodiment 22. Compounds according to either Embodiment 21 or 21A, ofthe formula:

wherein R₂₀ is H or methyl;

-   -   R₅₀ is H, or C₁-C₆ alkyl; and    -   R₅₅ is H, C₁-C₄ alkyl, phenyl, heteroaryl selected from the        group consisting of pyridyl, pyrimidyl, benzofuranyl, furanyl or        indolyl, or C₃-C₆ cycloalkyl.

Embodiment 22A. Compounds according to Embodiment 22, wherein

-   -   R₅ is H, C₁-C₆ alkoxy, CF₃, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl,        morpholinyl, oxazolyl, pyrazolyl, thiomorpholinyl,        thiomorpholinyl S,S-dioxide, piperidinyl, pyrrolidinyl, halogen,        C₁-C₆ alkyl, phenyl optionally substituted with 1, 2, 3, 4 or 5        groups that are independently halogen, C₁-C₆ alkyl, or C₁-C₄        alkoxy, CN, —(C₁-C₄ alkyl)-SO₂-phenyl,    -   R₆ is H, C₁-C₆ alkoxy, halogen, C₁-C₆ alkyl, CF₃, OCF₃,        phenyl(C₁-C₄)alkoxy, phenyloxy, CO₂H, C₁-C₆ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl,        CN, C₂-C₆ alkenyl, wherein the above phenyl groups are        optionally substituted with 1, 2, 3, 4 or 5 groups that are        independently halogen, C₁-C₆ alkyl, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl,        or C₁-C₄ alkoxy;    -   R₇ is H, OH, C₁-C₆ alkoxy, —O—SO₂-phenyl, halogen, C₁-C₆ alkyl,        phenyloxy, CF₃, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NR₃₀R₃₁, —NHR′,        —NR′R″, —N(R₁₆)C(O)—R₁₇, thiazolyl(C₁-C₆)alkoxy,        pyridyl(C₁-C₆)alkoxy, oxazolyl(C₁-C₄)alkoxy,        pyrazolyl(C₁-C₄)alkoxy, wherein the thiazolyl, pyridyl,        oxazolyl, and pyrazolyl groups are optionally substituted with        1, 2, or 3 groups that are independently C₁-C₆ alkyl, C₁-C₆        alkoxy, or halogen, phenyl optionally substituted with 1, 2, 3,        4 or 5 groups that are independently halogen, C₁-C₆ alkyl, C₁-C₄        alkoxy, OCF₃, CN, CO₂H, C₁-C₆ alkoxycarbonyl, C(O)NH₂,        —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₆        thioalkoxy, —S(O)_(x)—R₂₅, or —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅;        wherein        -   x is 0, 1, or 2;        -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;

R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl),phenyl, or pyridyl; or

-   -   -   R₂₆, R₂₇ and the nitrogen to which they are attached            represent pyrrolidinyl, piperidinyl, piperazinyl,            morpholinyl, or imidazolidinyl        -   R₃₀ and R₃₁ are independently H, C₁-C₆ alkyl, phenyl,            benzyl, pyridyl, imidazolyl, thiazolyl, oxazolyl, or            indolyl, or        -   R₃₀, R₃₁, and the nitrogen to which they are attached form a            heterocycloalkyl ring containing from 3 to 7 ring members;        -   R₁₆ is H or C₁-C₆ alkyl;        -   R₁₇ is C₁-C₆ alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl,            pyrazinyl, thienyl, C₁-C₆ alkoxy, OH, phenyloxy, pyridyloxy,            pyrimidyloxy, pyridazyloxy, pyrazinyloxy, thienyloxy,            phenyl(C₁-C₄)alkoxy, or —NR₁₈R₁₉;

    -   R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl, pyridyl,        thienyl, piperidinyl, pyrrolidinyl, morpholinyl,        thiomorpholinyl, thiomorpholinyl 1,1-dioxide,        tetrahydro-thiopyranyl 1,1-dioxide, or phenyl(C₁-C₄) alkyl;

    -   R₈ is H, halogen, C₁-C₆ alkoxy, C₁-C₆ alkyl, —S(O)_(x)—R₂₅,        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or CO₂H;

    -   R₉ is H, halogen, C₁-C₆ alkoxy, C₁-C₆ alkyl,        -   R′ is H, C₁-C₆ alkyl, or C₁-C₆ alkanoyl, wherein the alkyl            portion of the alkyl and alkanoyl groups are optionally            substituted with halogen,        -   R″ is H or C₁-C₆ alkyl, wherein the alkyl group is            optionally substituted with halogen.

Embodiment 22B. Compounds according to Embodiment 22A, wherein

-   -   R₅ is H, C₁-C₄ alkoxy, CF₃, CO₂H, C₁-C₄ alkoxycarbonyl,        —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or        —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl;    -   R₆ is H, C₁-C₄ alkoxy, halogen, C₁-C₄ alkyl, CF₃, OCF₃, CO₂H,        C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,        —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, CN, or C₂-C₆ alkenyl;    -   R₈ is H, halogen, C₁-C₄ alkoxy, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, or        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅ or CO₂H; and    -   R₉ is H, halogen, C₁-C₄ alkoxy, or C₁-C₄ alkyl.

Embodiment 22C. Compounds according to Embodiment 22B, wherein R₃ is H,halogen, methyl, methoxy, CF₃, or CN; R₄ is halogen, methoxy, methyl,CF₃, OCF₃, or CN; R_(3′) is H, or halogen.

Embodiment 22D. Compounds according to Embodiment 22C, wherein R₇ is H,OH, C₁-C₄ alkoxy, halogen, C₁-C₄ alkyl, CF₃, CO₂H, C₁-C₆ alkoxycarbonyl,—C(O)NR₃₀R₃₁, thiazolyl(C₁-C₆)alkoxy, pyridyl(C₁-C₆)alkoxy,oxazolyl(C₁-C₄)alkoxy, pyrazolyl(C₁-C₄)alkoxy, wherein the thiazolyl,pyridyl, oxazolyl, and pyrazolyl groups are optionally substituted with1, 2, or 3 groups that are independently C₁-C₆ alkyl, C₁-C₆ alkoxy, orhalogen, or phenyl optionally substituted with 1, 2, 3, 4 or 5 groupsthat are independently halogen, C₁-C₆ alkyl, C₁-C₄ alkoxy, OCF₃, CO₂H,C₁-C₆ alkoxycarbonyl, CN, or C₁-C₆ thioalkoxy; and

-   -   R₃₀ and R₃₁ are independently H, C₁-C₆ alkyl, phenyl, or benzyl.

Embodiment 22D1. Compounds according to Embodiment 22C, wherein R₇ is—S(O)_(x)—R₂₅, or —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅

-   -   R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇;    -   R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄        alkyl), phenyl, or pyridyl; or    -   R₂₆, R₂₇ and the nitrogen to which they are attached represent        pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or        imidazolidinyl.

Embodiment 22D2. Compounds according to Embodiment 21D1, wherein R₂₅ isC₁-C₆ alkyl or OH.

Embodiment 22D3. Compounds according to Embodiment 21D1, wherein R₂₅ isC₁-C₄ alkyl or NR₂₆R₂₇; and R₂₆ and R₂₇ are independently H, C₁-C₆alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl.

Embodiment 22D4. Compounds according to Embodiment 22D1, wherein

-   -   R₂₅ is C₁-C₄ alkyl or NR₂₆R₂₇; and R₂₆, R₂₇ and the nitrogen to        which they are attached represent pyrrolidinyl, piperidinyl,        piperazinyl, morpholinyl, or imidazolidinyl;    -   R₅ is H, C₁-C₄ alkoxy, CF₃, CO₂H, C₁-C₄ alkoxycarbonyl;    -   R₆ is H, C₁-C₄ alkoxy, halogen, C₁-C₄ alkyl, CF₃, OCF₃, CO₂H,        C₁-C₄ alkoxycarbonyl, CN, or C₂-C₆ alkenyl;    -   R₈ is H, halogen, C₁-C₄ alkoxy, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, or        —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅; and    -   R₉ is H, halogen, C₁-C₃ alkoxy, or C₁-C₃ alkyl.

Embodiment 22E. Compounds according to Embodiment 22D, wherein R₇ is H,OH, C₁-C₄ alkoxy, halogen, C₁-C₄ alkyl, CF₃, CO₂H, —C(O)NR₃₀R₃₁, orC₁-C₄ alkoxycarbonyl; and R₃₀ and R₃₁ are independently H or C₁-C₆alkyl.

Embodiment 22F. Compounds according to Embodiment 22E, wherein R₇ is H,OH, methoxy, halogen, methyl, CF₃, CO₂H, —C(O) NR₃₀R₃₁, or C₁-C₂alkoxycarbonyl; and R₃₀ and R₃₁ are independently H or C₁-C₄ alkyl.

Embodiment 22G. Compounds according to Embodiment 22F, wherein R₇ isCO₂H, —C(O)NR₃₀R₃₁, or C₁-C₂ alkoxycarbonyl.

Embodiment 22H. Compounds according to Embodiment 22F, wherein R₇ is OH,methoxy, halogen, methyl, or CF₃.

Embodiment 22I. Compounds according to any one of Embodiments 22E, 22F,22G or 22H, wherein R₃ is H, or halogen; R₄ is halogen, methyl, CF₃, ormethoxy; and R_(3′) is H or halogen.

Embodiment 22J. Compounds according to Embodiment 22I, wherein R₅ is H,methoxy, CF₃, CO₂H, C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl,or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl;

-   -   R₆ is H, C₁-C₂ alkoxy, halogen, C₁-C₂ alkyl, CF₃, OCF₃, CO₂H,        C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or        —C(O)N(C₁-C₄) alkyl (C₁-C₄) alkyl;    -   R₈ is H or halogen (preferred halogens are F or Cl); and    -   R₉ is H or halogen (preferred halogens are F or Cl).

Embodiment 22K. Compounds according to Embodiment 22J wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl); and R_(3′) is H.In another aspect, R₄ is methyl. In still another aspect, R₄ is CF₃. Inyet another aspect, R₄ is Cl.

Embodiment 22L. Compounds according to Embodiment 22K, wherein R₅ is H,methoxy, CF₃, CO₂H, or C₁-C₂ alkoxycarbonyl; R₆ is H, methoxy, halogen,methyl, CF₃, OCF₃, CO₂H, or C₁-C₂ alkoxycarbonyl (in one aspect, C₂alkoxycarbonyl); R₈ is H, F or Cl; and R₉ is H, F or Cl.

Embodiment 22M. Compounds according to Embodiment 22C, wherein R₇ is H,—NHR′, —NR′R″ or —N(R₁₆)C(O)—R₁₇; R₁₆ is H or C₁-C₄ alkyl; R₁₇ is C₁-C₆alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, thienyl, C₁-C₆alkoxy, phenyloxy, pyridyloxy, pyrimidyloxy, pyridazyloxy, pyrazinyloxy,thienyloxy, phenyl(C₁-C₄)alkoxy, or —NR₁₈R₁₉; and R₈ and R₁₉ areindependently H, C₁-C₆ alkyl, phenyl, pyridyl, thienyl, piperidinyl,pyrrolidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl 1,1-dioxide,tetrahydro-thiopyranyl 1,1-dioxide, or phenyl(C₁-C₄) alkyl; wherein R′is H, C₁-C₄ alkyl, or C₁-C₄ alkanoyl; R″ is C₁-C₄ alkyl, wherein thealkyl group is optionally substituted with halogen.

Embodiment 22N. Compounds according to Embodiment 22M, wherein R₃ is H,or halogen; R₄ is halogen, methyl, CF₃, or methoxy; and R_(3′) is H orhalogen. In another aspect, R₄ is methyl. In still another aspect, R₄ isCF₃. In yet another aspect, R₄ is Cl.

Embodiment 22O. Compounds according to Embodiment 22N, wherein R₅ is H,methoxy, CF₃, CO₂H, C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl;

-   -   R₆ is H, C₁-C₂ alkoxy, halogen, C₁-C₂ alkyl, CF₃, OCF₃, CO₂H,        C₁-C₂ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or        —C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl; R₈ is H or halogen (preferred        halogens are F or Cl); and R₉ is H or halogen (preferred        halogens are F or Cl).

Embodiment 22P. Compounds according to Embodiment 22O wherein R₃ is H;R₄ is halogen (preferably F or Cl, more preferably Cl), methyl, or CF₃;and R_(3′) is H.

Embodiment 22Q. Compounds according to Embodiment 22P, wherein R₅ is H,methoxy, CF₃, CO₂H, or C₁-C₂ alkoxycarbonyl;

-   -   R₆ is H, methoxy, halogen, methyl, CF₃, OCF₃, CO₂H, or C₁-C₂        alkoxycarbonyl (in one aspect, C₂ alkoxycarbonyl);    -   R₈ is H, F or Cl; and    -   R₉ is H, F or Cl.

Embodiment 22R. Compounds according to any one of Embodiments 22N, 22O,22P, or 22Q, wherein R₇ is H or —N(R₁₆)C(O)—R₁₇; wherein R₁₆ is H orC₁-C₄ alkyl; R₁₇ is C₁-C₆ alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl,pyrazinyl, thienyl, C₁-C₆ alkoxy, phenyloxy, pyridyloxy, pyrimidyloxy,pyridazyloxy, pyrazinyloxy, thienyloxy, phenyl(C₁-C₄)alkoxy, or—NR₁₈R₁₉; and R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl,pyridyl, thienyl, piperidinyl, pyrrolidinyl, morpholinyl,thiomorpholinyl, thiomorpholinyl 1,1-dioxide, tetrahydro-thiopyranyl1,1-dioxide, or phenyl(C₁-C₄) alkyl.

Embodiment 22S. Compounds according to Embodiment 22R, wherein R₁₇ isC₁-C₄ alkyl, phenyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, thienyl,C₁-C₄ alkoxy, phenyloxy, pyridyloxy, pyrimidyloxy, pyridazyloxy,pyrazinyloxy, thienyloxy, phenyl (C₁-C₄) alkoxy.

Embodiment 22T. Compounds according to Embodiment 22S, wherein R₁₇ isC₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl, phenyloxy, or phenyl (C₁-C₂) alkoxy.

Embodiment 22U. Compounds according to Embodiment 22S, wherein R₁₇ ispyridyl, pyrimidyl, pyridazyl, pyrazinyl, thienyl, pyridyloxy,pyrimidyloxy, pyridazyloxy, pyrazinyloxy, or thienyloxy.

Embodiment 22V. Compounds according to Embodiment 22R, wherein R₁₇ is—NR₁₈R₁₉; and R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl,pyridyl, thienyl, piperidinyl, pyrrolidinyl, morpholinyl,thiomorpholinyl, thiomorpholinyl 1,1-dioxide, tetrahydro-thiopyranyl1,1-dioxide, or phenyl(C₁-C₄) alkyl.

Embodiment 22W. Compounds according to Embodiment 22V, wherein R₁₇ is—NR₁₈R₁₉; and R₁₈ and R₁₉ are independently H, C₁-C₆ alkyl, phenyl,pyridyl, thienyl, piperidinyl, pyrrolidinyl, morpholinyl, orphenyl(C₁-C₄) alkyl.

Embodiment 22X. Compounds according to Embodiment 22W, wherein R₁₈ andR₁₉ are independently H, C₁-C₄ alkyl, phenyl, or phenyl(C₁-C₂) alkyl.

Embodiment 22Y. Compounds according to Embodiment 22V, wherein R₁₈ andR₁₉ are independently H, pyridyl, thienyl, piperidinyl, pyrrolidinyl,morpholinyl, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, ortetrahydro-thiopyranyl 1,1-dioxide. In another aspect, one of R₁₈ andR₁₉ is H.

Embodiment 22Z. Compounds according to Embodiment 22V, wherein R₁₈ andR₁₉ are independently H, pyridyl, piperidinyl, pyrrolidinyl, ormorpholinyl. In another aspect, one of R₁₈ and R₁₉ is H. In anotheraspect, only one of R₁₈ and R₁₉ is H.

Embodiment 22AA. Compounds according to Embodiment 21V, wherein R₁₈ andR₁₉ are independently H, thienyl, thiomorpholinyl, thiomorpholinyl1,1-dioxide, or tetrahydro-thiopyranyl 1,1-dioxide. In another aspect,one of R₁₈ and R₁₉ is H. In another aspect, only one of R₁₈ and R₁₉ isH.

Embodiment 22BB. Compounds according to any one of Embodiments 22I, 22J,22K, or 22L, wherein R₇ is H, —NHR′, or —NR′R″; wherein R′ is H, C₁-C₄alkyl, or C₁-C₄ alkanoyl; R″ is C₁-C₄ alkyl, wherein the alkyl group isoptionally substituted with halogen.

Embodiment 22CC. Compounds according to Embodiment 22D, wherein R₇ isthiazolyl(C₁-C₄)alkoxy, pyridyl(C₁-C₄)alkoxy, oxazolyl(C₁-C₄)alkoxy,pyrazolyl(C₁-C₄) alkoxy, wherein the thiazolyl, pyridyl, oxazolyl, andpyrazolyl groups are optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, or halogen.

Embodiment 22DD. Compounds according to Embodiment 21CC, wherein R₇ isthiazolyl(C₁-C₂)alkoxy, pyridyl(C₁-C₂)alkoxy, oxazolyl(C₁-C₂)alkoxy, orpyrazolyl(C₁-C₂)alkoxy, wherein the thiazolyl, pyridyl, oxazolyl, andpyrazolyl groups are optionally substituted with 1, or 2 groups that areindependently methyl, methoxy, or halogen.

Embodiment 22EE. Compounds according to Embodiment 22D, wherein R₇ isphenyl optionally substituted with 1, 2, 3, 4 or 5 groups that areindependently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, OCF₃, CN, CO₂H, C₁-C₄alkoxycarbonyl, C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C4)alkyl, or C₁-C₄ thioalkoxy. In another aspect,the phenyl is optionally substituted with 1, 2, or 3 groups, which areindependently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, OCF₃, CN, CO₂H, C₁-C₄alkoxycarbonyl, C(O)NH₂, —C(O)NH(C₁-C₄)alkyl, or—C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl.

Embodiment 22FF. Compounds according to Embodiment 22D, wherein R₇ isphenyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, OCF₃, CN, CO₂H, C₁-C₂alkoxycarbonyl, C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, or—C(O)N(C₁-C₄)alkyl(C₁-C₄)alkyl. In another aspect, the phenyl isoptionally substituted with 1 or 2 groups, which are independentlyhalogen, methyl, methoxy, CO₂H, C₁-C₂ alkoxycarbonyl, C(O)NH₂,—C(O)NH(C₁-C₄)alkyl, or —C(O)N(C₁-C₄) alkyl (C₁-C₄) alkyl.

Embodiment 22GG. Compounds according to Embodiment 22, wherein R₅, R₆,and the carbons to which they are attached form a phenyl ring, which isoptionally substituted with 1 or 2 groups that are independentlyhalogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, or OCF₃; and R₇, R₈, and R₉ areH.

Embodiment 22HH. Compounds according to Embodiment 22, wherein R₅, R₈,and R₉ are H; and R₆, R₇, and the carbons to which they are attachedform a phenyl ring, which is optionally substituted with 1 or 2 groupsthat are independently halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, or OCF₃.

Embodiment 22II. Compounds according to Embodiment 22, wherein R₅, R₆,and R₉ are H; and R₇ and R₈ are —O—CH₂CH₂—O—, or —O—CH₂—O—.

Embodiment 22JJ. Compounds according to Embodiment 22, wherein R₅, R₆,and R₉ are H; and R₇ and R₈ are —O—CH₂CH₂—O—.

Embodiment 22KK. Compounds according to Embodiment 22, wherein R₅, R₆,and R₉ are H; and R₇ and R₈ are —O—CH₂—O—.

Embodiment 22LL. Compounds according to any one of Embodiments 22GG,22HH, 22II, 22JJ, or 22KK wherein R₃ is H, halogen, methyl, methoxy,CF₃, or CN; R₄ is halogen, methoxy, methyl, CF₃, OCF₃, or CN; R_(3′) isH, or halogen.

Embodiment 22MM. Compounds according to Embodiment 22LL, wherein R₃ isH, or halogen(in one aspect F or Cl); R₄ is halogen (in one aspect F orCl), methyl, CF₃, or methoxy; and

-   -   R_(3′) is H or halogen (in one aspect F or Cl). In another        aspect, R₄ is methyl. In still another aspect, R₄ is CF₃. In yet        another aspect, R₄ is Cl.

Embodiment 22NN. Compounds according to any one of Embodiments 22A, 22B,22C, 22D, 22D1, 22D2, 22D3, 22D4, 22E, 22F, 22G, 22H, 22I, 22J, 22K,22L, 22M, 22N, 22O, 22P, 22Q, 22R, 22S, 22T, 22U, 22V, 22X, 22Y, 22Z,22AA, 22BB, 22CC, 22DD, 22EE, 22FF, 22GG, 22HH, 22II, 22JJ, 22KK, 22LL,or 22MM wherein R₅₀ is H, methyl, ethyl, n-propyl, isopropyl, sec-butyl,or isobutyl; and R₅₅ is H, methyl, ethyl or cyclopropyl.

Embodiment 22OO. Compounds according to Embodiment 22NN, wherein R₅₅ isH.

Embodiment 22PP. Compounds according to Embodiment 22NN, wherein R₅₀ ismethyl, ethyl, or n-propyl.

Embodiment 22RR. Compounds according to Embodiment 22NN, wherein R₅₀ isisopropyl, sec-butyl, or isobutyl.

Embodiment 22SS. Compounds according to Embodiment 22NN, wherein R₅₀ isn-propyl, isopropyl, or isobutyl.

Embodiment 22TT. Compounds according to Embodiment 22NN, wherein R₅₅ ismethyl.

Embodiment 22UU. Compounds according to Embodiment 22NN, wherein R₅₀ ismethyl, ethyl, or n-propyl.

Embodiment 22VV. Compounds according to Embodiment 22NN, wherein R₅₀ isisopropyl, sec-butyl, or isobutyl.

Embodiment 22WW. Compounds according to Embodiment 22NN, wherein R₅₀ isn-propyl, isopropyl, or isobutyl.

Embodiment 22XX. Compounds according to Embodiment 22NN, wherein R₅₅ isethyl.

Embodiment 22YY. Compounds according to Embodiment 22NN, wherein R₅₀ ismethyl, ethyl, or n-propyl.

Embodiment 22ZZ. Compounds according to Embodiment 22NN, wherein R₅₀ isisopropyl, sec-butyl, or isobutyl.

Embodiment 22AAA. Compounds according to Embodiment 22NN, wherein R₅₀ isn-propyl, isopropyl, or isobutyl.

Embodiment 22BBB. Compounds according to Embodiment 22NN, wherein R₅₅ iscyclopropyl.

Embodiment 22CCC. Compounds according to Embodiment 22NN, wherein R₅₀ ismethyl, ethyl, or n-propyl.

Embodiment 22DDD. Compounds according to Embodiment 22NN, wherein R₅₀ isisopropyl, sec-butyl, or isobutyl.

Embodiment 22EEE. Compounds according to Embodiment 22NN, wherein R₅₀ isn-propyl, isopropyl, or isobutyl.

Embodiment 22FFF. Compounds according to Embodiment 22N of the formula:

Embodiment 22GGG. Compounds according to Embodiment 22M, wherein R₅, R₉, R₃ and R_(3′) are H.

Embodiment 22HHH. Compounds according to Embodiment 22N, wherein R₄ ishalogen (in one aspect, F or Cl), methyl, or CF₃. In another aspect, R₄is methyl. In still another aspect, R₄ is CF₃. In yet another aspect, R₄is Cl.

In embodiment 23, the invention provides pharmaceutical compositionscomprising at least one compound of Formula 1 and at least onepharmaceutically acceptable carrier, solvent, adjuvant or excipient, ora combination thereof.

In embodiment 24, the invention provides a method of treating a patientwho has, or in preventing a patient from getting, a disease or conditionselected from the group consisting of Alzheimer's disease, for helpingprevent or delay the onset of Alzheimer's disease, for treating patientswith mild cognitive impairment (MCI) and preventing or delaying theonset of Alzheimer's disease in those who would progress from MCI to AD,for treating Down's syndrome, for treating humans who have HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treatingcerebral amyloid angiopathy and preventing its potential consequences,i.e. single and recurrent lobar hemorrhages, for treating otherdegenerative dementias, including dementias of mixed vascular anddegenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, age related maculardegeneration, or diffuse Lewy body type of Alzheimer's disease and whois in need of such treatment which comprises administration of atherapeutically effective amount of at least one compound of Formula I.

The following list is presented to give the reader an understanding ofthe compounds that are encompassed within the invention.

(S)-4-chloro-N-cinnamyl-N-(1-hydroxy-4-methylpentan-2-yl)benzenesulfonamide;

[(4-Chloro-benzenesulfonyl)-methyl-amino]-acetic acid ethyl ester;

[2-(4-Chloro-benzenesulfonylimino)-imidazolidin-1-yl]-acetic acid;

2-(4-Chloro-benzenesulfonylamino)-N-methyl-propionamide;

2-[(4-Chloro-benzenesulfonyl)-(3,4-dimethoxy-benzyl)-amino]-3-phenyl-propionamide;

2-[(4-Chloro-benzenesulfonyl)-(3-phenyl-propyl)-amino]-3-hydroxy-N-methyl-butyramide;

3-[(4-Chloro-benzenesulfonyl)-(3,4-dimethoxy-benzyl)-amino]-piperidine-1-carboxylicacid tert-butyl ester;

4-Chloro-N-(1,2-dimethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1,2-dimethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(l-ethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1,2,3,4-tetrahydro-naphthalen-2-yl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(2-pentyl-3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-butyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(4-methoxy-benzyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-methyl-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-propyl-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-pentyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-pentyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-chloro-N-(2,3-dihydro-1,4-benzodioxin—6-ylmethyl)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;

4-Chloro-N-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(2,3-dihydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(2,3-dihydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(2,4-dichloro-benzyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(2,4-dichloro-benzyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(2,4-difluoro-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-chloro-N-(2,4-difluorobenzyl)-N-[(1R)-1-(hydroxymethyl)-3-methyl-butyl]benzenesulfonamide;

4-Chloro-N-(2-cyano-ethyl)-N-cyclopropyl-benzenesulfonamide;

4-Chloro-N-(2-cyano-ethyl)-N-cyclopropyl-benzenesulfonamide;

4-Chloro-N-(2-cyano-ethyl)-N-ethyl-benzenesulfonamide;

4-Chloro-N-(2-cyano-ethyl)-N-ethyl-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-cyclohexylmethyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2-hydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-methyl-propyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-methyl-propyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-propyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-naphthalen-1-yl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-naphthalen-1-yl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl—4,5-dihydro-1H-pyrazol-3-yl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl—4,5-dihydro-1H-pyrazol-3-yl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,3-dimethyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,3-dimethyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-hydroxy-1-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxy-2,2-dimethyl-propyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxymethyl-bicyclo[2.2.1]hept-2-yl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(4-methyl-cyclohexyl)-benzenesulfonamide;

4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1R,2S)-2-hydroxy-1-(hydroxymethyl)-2-phenylethyl]benzenesulfonamide;

4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;

4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S)-1-(hydroxymethyl)propyl]benzenesulfonamide;

4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide;

4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]benzenesulfonamide;

4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S,3R,4R)-3-(hydroxymethyl)bicyclo[2.2.1]hept-2-yl]benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1-(4-methanesulfonyl-phenyl)-ethyl]-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1-(4-methanesulfonyl-phenyl)-ethyl]-benzenesulfonamide;

4-Chloro-N-(3-fluoro-4-methoxy-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-chloro-N-(3-fluoro-4-methoxybenzyl)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;

4-Chloro-N-(3-hydroxy-butyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-(4-chloro-6-fluoro-2H-chromen-3-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(4-chloro-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-chloro-N-(4-chlorobenzyl)-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;

4-Chloro-N-(4-diethylamino-1-methyl-butyl)-N-(3,4-dimethoxy-benzyl)-benzenesulfonamide;

4-Chloro-N,N-dicyclohexyl-benzenesulfonamide;

4-Chloro-N,N-diisopropyl-benzenesulfonamide;

4-Chloro-N,N-divinyl-benzenesulfonamide;

4-chloro-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]-N-(3-phenylpropyl)benzenesulfonamide;

4-chloro-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]-N-(4-methoxybenzyl)benzenesulfonamide;

4-chloro-N-[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N-methylbenzenesulfonamide;

4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-[(2E)-2-methyl-3-phenylprop-2-en-1-yl]benzenesulfonamide;

4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-[(2E)-3-phenylprop-2-en-1-yl]benzenesulfonamide;

4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-{3-methoxy-4-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]benzyl}benzenesulfonamide;

4-chloro-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N-methylbenzenesulfonamide;

4-Chloro-N-[2-(3,4-dihydroxy-phenyl)-2-oxo-ethyl]-N-methylbenzenesulfonamide;

4-chloro-N-{[(1R,2S)-2-hydroxycyclohexyl]methyl}-N-{3-methoxy-4-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]benzyl}benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methylsulfanyl-propyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(4-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-pyridin-2-ylmethyl-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-prop-2-ynyl-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(tetrahydro-furan-2-ylmethyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methoxy-propyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(1-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-allyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methylsulfanyl-propyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(4-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-pyridin-2-ylmethyl-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-prop-2-ynyl-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(tetrahydro-furan-2-ylmethyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methoxy-propyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(1-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-allyl)-benzenesulfonamide;

4-Chloro-N-cyanomethyl-N-methyl-benzenesulfonamide;

4-Chloro-N-cyclohexyl-N-(2-hydroxy-ethyl)-benzenesulfonamide;

4-Chloro-N-cyclohexyl-N-(2-hydroxy-ethyl)-benzenesulfonamide;

4-Chloro-N-cyclohexyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-cyclohexyl-N-isopropyl-benzenesulfonamide;

4-Chloro-N-cyclooctyl-N-(3,4-dimethoxy-benzyl)-benzenesulfonamide;

4-Chloro-N-cyclopentyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-cyclopentyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-cyclopropylmethyl-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-cyclopropylmethyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-cyclopropylmethyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-ethyl-N-(2-pyridin-2-yl-ethyl)-benzenesulfonamide;

4-Chloro-N-ethyl-N-[2-hydroxy-2-(3-hydroxy-phenyl)-ethyl]-benzenesulfonamide;

4-Chloro-N-ethyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

4-Chloro-N-isopropyl-N-(2-pyridin-4-yl-ethyl)-benzenesulfonamide;

4-Chloro-N-methyl-N-(1-methyl-piperidin-4-yl)-benzenesulfonamide;

4-Chloro-N-methyl-N-(1-methyl-piperidin-4-yl)-benzenesulfonamide;

4-Chloro-N-methyl-N-(2-pyridin-4-yl-ethyl)-benzenesulfonamide;

4-Chloro-N-pyrrolidin-3-yl-benzenesulfonamide;

N-(1,3-benzodioxol-5-ylmethyl)-4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;

N-(1-Benzyl-pyrrolidin-3-yl)-4-chloro-N-ethyl-benzenesulfonamide;

N-(2-Amino-benzyl)-4-chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;

N-(2-Benzyl-cyclohexyl)-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

N-(4-Bromo-benzyl)-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

N-(4-bromobenzyl)-4-chloro-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;

N,N-Di-sec-butyl-4-chloro-benzenesulfonamide;

N-[(1R)-1-benzyl-2-hydroxyethyl]-4-chloro-N-(3,4-dimethoxybenzyl)benzenesulfonamide;

N-[(1S)-1-benzyl-2-hydroxyethyl]-4-chloro-N-(3,4-dimethoxybenzyl)benzenesulfonamide;

N-[(4-chlorophenyl)sulfonyl]-N-(3,4-dimethoxybenzyl)-L-phenylalaninamide;

N-[3-(4-tert-Butyl-phenyl)-2-methyl-propyl]-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

N2-[(4-chlorophenyl)sulfonyl]-N1-methyl-L-alaninamide;

N-Allyl-4-chloro-N-cyclohexyl-benzenesulfonamide;

N-Benzo[1,3]dioxol-5-ylmethyl-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

N-Benzofuran-2-ylmethyl-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

N-Benzofuran-2-ylmethyl-N-sec-butyl-4-chloro-benzenesulfonamide;

N-Benzyl-4-chloro-N-(1-hydroxymethyl-propyl)-benzenesulfonamide;

N-Benzyl-4-chloro-N-(2-hydroxy-cyclohexyl)-benzenesulfonamide;

N-Benzyl-4-chloro-N-(2-hydroxymethyl-cyclohexyl)-benzenesulfonamide;

N-benzyl-4-chloro-N-[(1R)-1-(hydroxymethyl)propyl]benzenesulfonamide;

N-benzyl-4-chloro-N-[(1S,2R)-2-(hydroxymethyl)cyclohexyl]benzenesulfonamide;

N-benzyl-4-chloro-N-[(1S,2S)-2-hydroxycyclohexyl]benzenesulfonamide;

N-Benzyl-N-sec-butyl-4-chloro-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(2-pentyl-3-phenyl-allyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(3,3-diphenyl-allyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(3-phenyl-allyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(3-phenyl-butyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(3-phenyl-propyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(4,6-dichloro-2H-chromen-3-ylmethyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-(4-chloro-6-fluoro-2H-chromen-3-ylmethyl)-benzenesulfonamide;

N-sec-Butyl-4-chloro-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;

N-tert-Butyl-2-(4-chloro-benzenesulfonylamino)-3-methyl-butyramide; orpharmaceutically acceptable salts thereof.

Specific representative examples of compounds of the invention are thefollowing.

4-Chloro-N-cyclooctyl-N-(3,4-dimethoxy-benzyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,3-dimethyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(4-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-methyl-propyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxy-2,2-dimethyl-propyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1-(4-methanesulfonyl-phenyl)-ethyl]-benzenesulfonamide;

3-[(4-Chloro-benzenesulfonyl)-(3,4-dimethoxy-benzyl)-amino]-piperidine-1-carboxylicacid tert-butyl ester;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxymethyl-bicyclo[2.2.1]hept-2-yl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(R-2-hydroxy-1-phenyl-ethyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(R-1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;

N-Benzyl-4-chloro-N-(1S,2S-2-hydroxy-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-3-phenyl-allyl)-benzenesulfonamide;

N-Benzo[1,3]dioxol-5-ylmethyl-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(3-fluoro-4-methoxy-benzyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(4-methoxy-benzyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(4-chloro-benzyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

N-(4-Bromo-benzyl)-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(2,4-difluoro-benzyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

R-N-sec-Butyl-4-chloro-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(R-1,2-dimethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

3-[(4-Chloro-benzenesulfonyl)-(3-phenyl-allyl)-amino]-piperidine-1-carboxylicacid tert-butyl ester;

4-[(4-Chloro-benzenesulfonyl)-(3-phenyl-allyl)-amino]-piperidine-1-carboxylicacid ethyl ester;

R-N-sec-Butyl-4-chloro-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(R-1,2-dimethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

2S,3R-2-[(4-Chloro-benzenesulfonyl)-(3-phenyl-propyl)-amino]-3-hydroxy-N-methyl-butyramide;

4-Chloro-N-(1S,2S-2-hydroxy-cyclopentyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-[(4-Chloro-benzenesulfonyl)-(3-phenyl-propyl)-amino]-piperidine-1-carboxylicacid ethyl ester;

N-[3-(4-tert-Butyl-phenyl)-2-methyl-propyl]-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(4-chloro-6-fluoro-2H-chromen-3-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-pentyl-3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;

N-Benzofuran-2-ylmethyl-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-butyl)-benzenesulfonamide;

4-Chloro-N-cyclopropylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

R-N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;

R-N-sec-Butyl-4-chloro-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;

R-N-Benzofuran-2-ylmethyl-N-sec-butyl-4-chloro-benzenesulfonamide;

R-N-sec-Butyl-4-chloro-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;

R-N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(3-fluoro-4-methoxy-benzyl)-benzenesulfonamide;

4-Chloro-N-(2,4-difluoro-benzyl)-N-(2,5-dimethyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(4-methoxy-benzyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,5-dimethyl-cyclohexyl)-benzenesulfonamide;

N-(4-Bromo-benzyl)-4-chloro-N-(2,5-dimethyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(2-methyl-3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1R,2S,5R-2-isopropyl-5-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;

N-(2-Benzyl-cyclohexyl)-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1,2,3,4-tetrahydro-naphthalen-2-yl)-benzenesulfonamide;

4-Chloro-N-(4,6-dichloro-2H-chromen-3-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;

4-Chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-propyl-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-methyl-benzenesulfonamide;

R-N-sec-Butyl-4-chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1,2-dimethyl-propyl)-benzenesulfonamide;

4-Chloro-N-(S-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-[(4-Chloro-benzenesulfonyl)-(R-1-hydroxymethyl-3-methyl-butyl)-amino]-3-methyl-but-2-enoicacid ethyl ester;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-naphthalen-2-ylmethyl-benzenesulfonamide;

4-Chloro-N-furan-2-ylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-furan-3-ylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(S-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

4-Chloro-N-(S-1,2-dimethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;

N-(2-Bromo-3-phenyl-allyl)-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

N-But-2-enyl-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-pentyl-benzenesulfonamide;

4-Chloro-N-(3-furan-2-yl-2-methyl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(3-furan-2-yl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-pentyl)-benzenesulfonamide;

4-Chloro-N-(2-ethyl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(2-ethyl-butyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-methyl-but-2-enyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-pyridin-3-yl-allyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-[3-(2-nitro-phenyl)-allyl]-benzenesulfonamide;

4-[(4-Chloro-benzenesulfonyl)-(R-1-hydroxymethyl-3-methyl-butyl)-amino]-but-2-enoicacid ethyl ester;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-4-phenyl-pentyl)-benzenesulfonamide;

4-Chloro-N-cyclohexylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(2-chloro-3-phenyl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-[3-(3-chloro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-p-tolyl-allyl)-benzenesulfonamide;

4-Chloro-N-[3-(4-dimethylamino-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-[3-(4-fluoro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-m-tolyl-allyl)-benzenesulfonamide;

4-Chloro-N-[3-(3-fluoro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-o-tolyl-allyl)-benzenesulfonamide;

4-Chloro-N-[3-(4-chloro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-[3-(2-fluoro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;

4-Chloro-N-(6-methoxy-pyridin-3-ylmethyl)-N-(2-methyl-cyclohexyl)-benzenesulfonamide;

4-Chloro-N-(6-chloro-pyridin-3-ylmethyl)-N-(2-methyl-cyclohexyl)-benzenesulfonamide;

N-(6-Bromo-pyridin-3-ylmethyl)-4-chloro-N-(2-methyl-cyclohexyl)-benzenesulfonamide;and

4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-pyridin-3-yl-allyl)-benzenesulfonamide.

In another aspect, the compounds of the invention have minimalinteraction or preferably, no interaction with notch.

Definitions

The definitions and explanations below are for the terms as usedthroughout this entire document including both the specification and theclaims.

It should be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the content clearly dictates otherwise. Thus, for example,reference to a composition containing “a compound” includes a mixture oftwo or more compounds. It should also be noted that the term “or” isgenerally employed in its-sense including “and/or” unless the contentclearly dictates otherwise.

Where multiple substituents are indicated as being attached to astructure, it is to be understood that the substituents can be the sameor different. Thus for example “R_(m)optionally substituted with 1, 2 or3 R_(q) groups” indicates that R_(m)is substituted with 1, 2, or 3 R_(q)groups where the R_(q) groups can be the same or different.

APP, amyloid precursor protein, is defined as any APP polypeptide,including APP variants, mutations, and isoforms, for example, asdisclosed in U.S. Pat. No. 5,766,846. A beta, amyloid beta peptide, isdefined as any peptide resulting from beta-secretase mediated cleavageof APP, including peptides of 39, 40, 41, 42, and 43 amino acids, andextending from the beta-secretase cleavage site to amino acids 39, 40,41, 42, or 43.

Pharmaceutically acceptable refers to those properties and/or substancesthat are acceptable to the patient from a toxicological and/or safetypoint of view.

A therapeutically effective amount is defined as an amount effective toreduce or lessen at least one symptom of the disease being treated or toreduce or delay onset of one or more clinical markers or symptoms of thedisease.

By “alkyl” and “C₁-C₆ alkyl” in the present invention is meant straightor branched chain alkyl groups having 1-6 carbon atoms, such as, methyl,ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl,2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and3-methylpentyl. It is understood that in cases where an alkyl chain of asubstituent (e.g. of an alkyl, alkoxy or alkenyl group) is shorter orlonger than 6 carbons, it will be so indicated in the second “C” as, forexample, “C₁-C₁₀”,) indicates a maximum of 10 carbons.

By “alkoxy” and “C₁-C₆ alkoxy” in the present invention is meantstraight or branched chain alkyl groups having 1-6 carbon atoms,attached through at least one divalent oxygen atom, such as, forexample, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy,tert-butoxy, pentoxy, isopentoxy, neopentoxy, hexoxy, and3-methylpentoxy.

By the term “halogen” in the present invention is meant fluorine,bromine, chlorine, and/or iodine.

“Alkenyl” and “C₂-C₆ alkenyl” means straight and branched hydrocarbonradicals having from 2 to 6 carbon atoms and from one to three doublebonds and includes, for example, ethenyl, propenyl, 1-but-3-enyl,1-pent-3-enyl, 1-hex-5-enyl and the like. “Alkynyl” and “C₂-C₆ alkynyl”means straight and branched hydrocarbon radicals having from 2 to 6carbon atoms and one or two triple bonds and includes ethynyl, propynyl,butynyl, pentyn-2-yl and the like.

As used herein, the term “cycloalkyl” refers to saturated carbocyclicradicals having three to twelve carbon atoms. The cycloalkyl can bemonocyclic, a polycyclic fused system, or a bi or polycyclic bridgedsystem, such as adamantyl or bicyclo[2.2.1] heptyl. Examples of suchradicals include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.Preferred cycloalkyl groups are cyclopentyl, cyclohexyl, andcycloheptyl. The cycloalkyl groups herein are unsubstituted or, asspecified, substituted in one or more substitutable positions withvarious groups. For example, such cycloalkyl groups may be optionallysubstituted with, for example, C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen,hydroxy, cyano, nitro, amino, mono (C₁-C₆)alkylamino,di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆ haloalkyl, C₁-C₆haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino(C₁-C₆)alkyl ordi(C₁-C₆)alkylamino(C₁-C₆)alkyl.

By “aryl” is meant an aromatic carbocyclic group having a single ring(e.g., phenyl) or multiple condensed rings in which at least one isaromatic, (e.g., 1,2,3,4-tetrahydronaphthyl, naphthyl), which isoptionally mono-, di-, or trisubstituted. Preferred aryl groups of thepresent invention are phenyl, 1-naphthyl, 2-naphthyl, indanyl, indenyl,dihydronaphthyl, fluorenyl, tetralinyl or6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl. The aryl groups herein areunsubstituted or, as specified, substituted in one or more substitutablepositions with various groups. For example, such aryl groups may beoptionally substituted with, for example, C₁-C₆ alkyl, C₁-C₆ alkoxy,halogen, hydroxy, cyano, nitro, amino, mono(C₁-C₆)alkylamino,di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆ haloalkyl, C₁-C₆haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino(C₁-C₆)alkyl ordi(C₁-C₆)alkylamino(C₁-C₆)alkyl.

By “heteroaryl” is mean at least one or more aromatic ring systems of5-, 6-, or 7-membered rings which includes fused ring systems of 9-11atoms containing at least one and up to four heteroatoms selected fromnitrogen, oxygen, or sulfur. Preferred heteroaryl groups of the presentinvention include pyridinyl, pyrimidinyl, quinolinyl, benzothienyl,indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl,quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl,pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl,benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl,thiadiazolyl, triazolyl, tetrazolyl, isothiazolyl, naphthyridinyl,isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl,isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl,benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl,benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, pteridinyl,benzothiazolyl, imidazopyridinyl, imidazothiazolyl,dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl,dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, chromonyl,chromanonyl, pyridinyl-N-oxide, tetrahydroquinolinyl, dihydroquinolinyl,dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl,dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl,pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinylN-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide,isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide,phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolylN-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide,benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide,oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolylN-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide. Theheteroaryl groups herein are unsubstituted or, as specified, substitutedin one or more substitutable positions with various groups. For example,such heteroaryl groups may be optionally substituted with, for example,C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen, hydroxy, cyano, nitro, amino,mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆alkynyl,C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl,mono(C₁-C₆)alkylamino(C₁-C₆)alkyl or di(C₁-C₆)alkylamino(C₁-C₆)alkyl.

By “heterocycle”, “heterocycloalkyl” or “heterocyclyl” is meant one ormore carbocyclic ring systems of 4-, 5-, 6-, or 7-membered rings whichincludes fused ring systems of 9-11 atoms containing at least one and upto four heteroatoms selected from nitrogen, oxygen, or sulfur. Preferredheterocycles of the present invention include morpholinyl,thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide,piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl,tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl,homopiperidinyl, homomorpholinyl, homothiomorpholinyl,homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl,dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl,dihydrofuryl, dihydropyranyl, tetrahydrothienyl S-oxide,tetrahydrothienyl S,S-dioxide and homothiomorpholinyl S-oxide. Theheterocycle groups herein are unsubstituted or, as specified,substituted in one or more substitutable positions with various groups.For example, such heterocycle groups may be optionally substituted with,for example, C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen, hydroxy, cyano, nitro,amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆ alkenyl, C₂-C₆alkynyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl,mono(C₁-C₆)alkylamino(C₁-C₆)alkyl, di(C₁-C₆)alkylamino(C₁-C₆)alkyl or═O.

Structures were named using Name Pro IUPAC Naming Software, version5.09, available from Advanced Chemical Development, Inc., 90 AdelaideStreet West, Toronto, Ontario, M5H 3V9, Canada or using ChemDraw v. 6.02or ChemDraw v. 8.03, both of which are available from Cambridgesoft at100 Cambridge Park Drive, Cambridge, Mass. 02140(www.cambridgesoft.com).

The compounds of this invention may contain one or more asymmetriccarbon atoms, so that the compounds can exist in differentstereoisomeric forms. These compounds can be, for example, racemates,chiral non-racemic or diastereomers. In these situations, the singleenantiomers, i.e., optically active forms, can be obtained by asymmetricsynthesis or by resolution of the racemates. Resolution of the racematescan be accomplished, for example, by conventional methods such ascrystallization in the presence of a resolving agent; chromatography,using, for example a chiral HPLC column; or derivatizing the racemicmixture with a resolving reagent to generate diastereomers, separatingthe diastereomers via chromatography, and removing the resolving agentto generate the original compound in enantiomerically enriched form. Anyof the above procedures can be repeated to increase the enantiomericpurity of a compound.

Non-toxic pharmaceutically acceptable salts include, but are not limitedto salts of inorganic acids such as hydrochloric, sulfuric, phosphoric,diphosphoric, hydrobromic, and nitric or salts of organic acids such asformic, citric, malic, maleic, fumaric, tartaric, succinic, acetic,lactic, methanesulfonic, p-toluenesulfonic, 2-hydroxyethylsulfonic,salicylic and stearic. Similarly, pharmaceutically acceptable cationsinclude, but are not limited to sodium, potassium, calcium, aluminum,lithium and ammonium. Those skilled in the art will recognize a widevariety of non-toxic pharmaceutically acceptable addition salts. Theinvention also encompasses prodrugs of the compounds of Formula I.

The invention also encompasses the acylated prodrugs of the compounds ofFormula I. Those skilled in the art will recognize various syntheticmethodologies, which may be employed to prepare non-toxicpharmaceutically acceptable addition salts and acylated prodrugs of thecompounds encompassed by Formula I.

When the compounds described herein contain olefinic double bonds orother centers of geometric asymmetry, and unless otherwise specified, itis intended that the compounds include the cis, trans, Z- andE-configurations. Likewise, all tautomeric forms are also intended to beincluded. The invention also encompasses the prodrugs of the compoundsof Formula I. Those skilled in the art will recognize various syntheticmethodologies that may be employed to prepare non-toxic pharmaceuticallyacceptable prodrugs of the compounds encompassed by Formula I. Thoseskilled in the art will recognize a wide variety of non-toxicpharmaceutically acceptable solvates, such as water, ethanol, mineraloil, vegetable oil, and dimethylsulfoxide.

The compounds of general Formula I may be administered orally,topically, parenterally, by inhalation or spray or rectally in dosageunit formulations containing conventional non-toxic pharmaceuticallyacceptable carriers, adjuvants and vehicles. The term parenteral as usedherein includes percutaneous, subcutaneous, intravascular (e.g.,intravenous), intramuscular, or intrathecal injection or infusiontechniques and the like. In addition, there is provided a pharmaceuticalformulation comprising a compound of general Formula I and apharmaceutically acceptable carrier. One or more compounds of generalFormula I may be present in association with one or more non-toxicpharmaceutically acceptable carriers and/or diluents and/or adjuvants,and if desired other active ingredients. The pharmaceutical compositionscontaining compounds of general Formula I may be in a form suitable fororal use, for example, as tablets, troches, lozenges, aqueous or oilysuspensions, dispersible powders or granules, emulsion, hard or softcapsules, or syrups or elixirs.

Compositions intended for oral use may be prepared according to anymethod known to the art for the manufacture of pharmaceuticalcompositions and such compositions may contain one or more agentsselected from the group consisting of sweetening agents, flavoringagents, coloring agents and preservative agents in order to providepharmaceutically elegant and palatable preparations. Tablets contain theactive ingredient in admixture with non-toxic pharmaceuticallyacceptable excipients that are suitable for the manufacture of tablets.These excipients may be for example, inert diluents, such as calciumcarbonate, sodium carbonate, lactose, calcium phosphate or sodiumphosphate; granulating and disintegrating agents, for example, cornstarch, or alginic acid; binding agents, for example starch, gelatin oracacia, and lubricating agents, for example magnesium stearate, stearicacid or talc. The tablets may be uncoated or they may be coated by knowntechniques. In some cases such coatings may be prepared by knowntechniques to delay disintegration and absorption in thegastrointestinal tract and thereby provide a sustained action over alonger period. For example, a time delay material such as glycerylmonosterate or glyceryl distearate may be employed.

Formulations for oral use may also be presented as hard gelatincapsules, wherein the active ingredient is mixed with an inert soliddiluent, for example, calcium carbonate, calcium phosphate or kaolin, oras soft gelatin capsules wherein the active ingredient is mixed withwater or an oil medium, for example peanut oil, liquid paraffin or oliveoil.

Formulations for oral use may also be presented as lozenges.

Aqueous suspensions contain the active materials in admixture withexcipients suitable for the manufacture of aqueous suspensions. Suchexcipients are suspending agents, for example sodiumcarboxymethylcellulose, methylcellulose, hydropropyl-methylcellulose,sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia;dispersing or wetting agents may be a naturally-occurring phosphatide,for example, lecithin, or condensation products of an alkylene oxidewith fatty acids, for example polyoxyethylene stearate, or condensationproducts of ethylene oxide with long chain aliphatic alcohols, forexample heptadecaethyleneoxycetanol, or condensation products ofethylene oxide with partial esters derived from fatty acids and ahexitol such as polyoxyethylene sorbitol monooleate, or condensationproducts of ethylene oxide with partial esters derived from fatty acidsand hexitol anhydrides, for example polyethylene sorbitan monooleate.The aqueous suspensions may also contain one or more preservatives, forexample ethyl, or n-propyl p-hydroxybenzoate, one or more coloringagents, one or more flavoring agents, and one or more sweetening agents,such as sucrose or saccharin.

Oily suspensions may be formulated by suspending the active ingredientsin a vegetable oil, for example arachis oil, olive oil, sesame oil orcoconut oil, or in a mineral oil such as liquid paraffin. The oilysuspensions may contain a thickening agent, for example beeswax, hardparaffin or cetyl alcohol. Sweetening agents and flavoring agents may beadded to provide palatable oral preparations. These compositions may bepreserved by the addition of an anti-oxidant such as ascorbic acid.

Dispersible powders and granules suitable for preparation of an aqueoussuspension by the addition of water provide the active ingredient inadmixture with a dispersing or wetting agent, suspending agent and oneor more preservatives. Suitable dispersing or wetting agents orsuspending agents are exemplified by those already mentioned above.Additional excipients, for example sweetening, flavoring and coloringagents, may also be present.

Pharmaceutical compositions of the invention may also be in the form ofoil-in-water emulsions. The oily phase may be a vegetable oil or amineral oil or mixtures of these. Suitable emulsifying agents may benaturally-occurring gums, for example gum acacia or gum tragacanth,naturally-occurring phosphatides, for example soy bean, lecithin, andesters or partial esters derived from fatty acids and hexitol,anhydrides, for example sorbitan monooleate, and condensation productsof the said partial esters with ethylene oxide, for examplepolyoxyethylene sorbitan monooleate. The emulsions may also containsweetening and flavoring agents.

Syrups and elixirs may be formulated with sweetening agents, for exampleglycerol, propylene glycol, sorbitol, glucose or sucrose. Suchformulations may also contain a demulcent, a preservative and flavoringand coloring agents. The pharmaceutical compositions may be in the formof a sterile injectable aqueous or oleaginous suspension. Thissuspension may be formulated according to the known art using thosesuitable dispersing or wetting agents and suspending agents that havebeen mentioned above. The sterile injectable preparation may also be asterile injectable solution or suspension in a non-toxic parentallyacceptable diluent or solvent, for example as a solution in1,3-butanediol. Among the acceptable vehicles and solvents that may beemployed are water, Ringer's solution and isotonic sodium chloridesolution. In addition, sterile, fixed oils are conventionally employedas a solvent or suspending medium. For this purpose any bland fixed oilmay be employed including synthetic mono- or diglycerides. In addition,fatty acids such as oleic acid find use in the preparation ofinjectables.

The compounds of general Formula I may also be administered in the formof suppositories, e.g., for rectal administration of the drug. Thesecompositions can be prepared by mixing the drug with a suitablenon-irritating excipient that is solid at ordinary temperatures butliquid at the rectal temperature and will therefore melt in the rectumto release the drug. Such materials include cocoa butter andpolyethylene glycols.

Compounds of general Formula I may be administered parenterally in asterile medium. The drug, depending on the vehicle and concentrationused, can either be suspended or dissolved in the vehicle.Advantageously, adjuvants such as local anesthetics, preservatives andbuffering agents can be dissolved in the vehicle.

For disorders of the eye or other external tissues, e.g., mouth andskin, the formulations are preferably applied as a topical gel, spray,ointment or cream, or as a suppository, containing the activeingredients in a total amount of, for example, 0.075 to 30% w/w,preferably 0.2 to 20% w/w and most preferably 0.4 to 15% w/w. Whenformulated in an ointment, the active ingredients may be employed witheither paraffinic or a water-miscible ointment base.

Alternatively, the active ingredients may be formulated in a cream withan oil-in-water cream base. If desired, the aqueous phase of the creambase may include, for example at least 30% w/w of a polyhydric alcoholsuch as propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol,polyethylene glycol and mixtures thereof. The topical formulation maydesirably include a compound which enhances absorption or penetration ofthe active ingredient through the skin or other affected areas. Examplesof such dermal penetration enhancers include dimethylsulfoxide andrelated analogs. The compounds of this invention can also beadministered by a transdermal device. Preferably topical administrationwill be accomplished using a patch either of the reservoir and porousmembrane type or of a solid matrix variety. In either case, the activeagent is delivered continuously from the reservoir or microcapsulesthrough a membrane into the active agent permeable adhesive, which is incontact with the skin or mucosa of the recipient. If the active agent isabsorbed through the skin, a controlled and predetermined flow of theactive agent is administered to the recipient. In the case ofmicrocapsules, the encapsulating agent may also function as themembrane. The transdermal patch may include the compound in a suitablesolvent system with an adhesive system, such as an acrylic emulsion, anda polyester patch. The oily phase of the emulsions of this invention maybe constituted from known ingredients in a known manner. While the phasemay comprise merely an emulsifier, it may comprise a mixture of at leastone emulsifier with a fat or oil or with both a fat and an oil.Preferably, a hydrophilic emulsifier is included together with alipophilic emulsifier, which acts as a stabilizer. It is also preferredto include both an oil and a fat. Together, the emulsifier(s) with orwithout stabilizer(s) make-up the so-called emulsifying wax, and the waxtogether with the oil and fat make up the so-called emulsifying ointmentbase, which forms the oily, dispersed phase of the cream formulations.Emulsifiers and emulsion stabilizers suitable for use in the formulationof the invention include Tween 60, Span 80, cetostearyl alcohol,myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate,among others. The choice of suitable oils or fats for the formulation isbased on achieving the desired cosmetic properties, since the solubilityof the active compound in most oils likely to be used in pharmaceuticalemulsion formulations is very low. Thus, the cream should preferably bea non-greasy, non-staining and washable product with suitableconsistency to avoid leakage from tubes or other containers. Straight orbranched chain, mono- or dibasic alkyl esters such as di-isoadipate,isocetyl stearate, propylene glycol diester of coconut fatty acids,isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate,2-ethylhexyl palmitate or a blend of branched chain esters may be used.These may be used alone or in combination depending on the propertiesrequired. Alternatively, high melting point lipids such as white softparaffin and/or liquid paraffin or other mineral oils can be used.

Formulations suitable for topical administration to the eye also includeeye drops wherein the active ingredients are dissolved or suspended insuitable carrier, especially an aqueous solvent for the activeingredients. The anti-inflammatory active ingredients are preferablypresent in such formulations in a concentration of 0.5 to 20%,advantageously 0.5 to 10% and particularly about 1.5% w/w. Fortherapeutic purposes, the active compounds of this combination inventionare ordinarily combined with one or more adjuvants appropriate to theindicated route of administration. If administered per os, the compoundsmay be admixed with lactose, sucrose, starch powder, cellulose esters ofalkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesiumstearate, magnesium oxide, sodium and calcium salts of phosphoric andsulfuric acids, gelatin, acacia gum, sodium alginate,polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted orencapsulated for convenient administration. Such capsules or tablets maycontain a controlled-release formulation as may be provided in adispersion of active compound in hydroxypropylmethyl cellulose.Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules having one or more of the carriers or diluents mentioned foruse in the formulations for oral administration. The compounds may bedissolved in water, polyethylene glycol, propylene glycol, ethanol, cornoil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodiumchloride, and/or various buffers. Other adjuvants and modes ofadministration are well and widely known in the pharmaceutical art.

Dosage levels of the order of from about 0.1 mg to about 140 mg perkilogram of body weight per day are useful in the treatment of theabove-indicated conditions (about 0.5 mg to about 7 g per patient perday). The amount of active ingredient that may be combined with thecarrier materials to produce a single dosage form will vary dependingupon the host treated and the particular mode of administration. Dosageunit forms will generally contain between from about 1 mg to about 500mg of an active ingredient. The daily dose can be administered in one tofour doses per day. In the case of skin conditions, it may be preferableto apply a topical preparation of compounds of this invention to theaffected area two to four times a day.

It will be understood, however, that the specific dose level for anyparticular patient will depend upon a variety of factors including theactivity of the specific compound employed, the age, body weight,general health, sex, diet, time of administration, route ofadministration, and rate of excretion, drug combination and the severityof the particular disease undergoing therapy.

For administration to non-human animals, the composition may also beadded to the animal feed or drinking water. It may be convenient toformulate the animal feed and drinking water compositions so that theanimal takes in a therapeutically appropriate quantity of thecomposition along with its diet. It may also be convenient to presentthe composition as a premix for addition to the feed or drinking water.

The disclosures in this document of all articles and references,including patents, are incorporated herein by reference in theirentirety.

The invention is illustrated further by the following examples, whichare not to be construed as limiting the invention in scope or spirit tothe specific procedures described in them.

The starting materials and various intermediates may be obtained fromcommercial sources, prepared from commercially available compounds, orprepared using known synthetic methods.

General Synthetic Procedures

The compounds of the invention can be prepared using methods well knownin the art of organic synthesis. Representative procedures suitable forpreparing compounds of the invention are outlined in the followingschemes.

Compounds of the invention can be prepared by various methods known tothose skilled in the art. For example, the compounds of the invention,as well as all intermediates, can be synthesized by known processesusing either solution or solid phase techniques, as shown below.

In scheme 1, the definitions of the variables are as defined above,except that R4 is an optionally substituted phenyl, wherein the phenylis optionally substituted with R₃, R_(3′), and/or R₄, wherein R₃,R_(3′), and R₄ are as defined above.

Using standard methods familiar to those skilled in the art, a reductivealkylation is performed by treating primary amine 1.0 with appropriatealdehydes or ketones in a suitable solvent such as methanol. Upontreatment with a reducing agent such as sodium borohydride, sodiumcyanoborohydride, or polystyrene bound borohydride, intermediate amines2.0 are formed. Amines 2.0 are further functionalized by treatment withan appropriate sulfonylhalide 3.0 (where X is a halogen) in a suitablesolvent, such as dichloromethane, THF or chloroform, in the presence ofa base such as diisopropylethylamine, triethylamine or pyridine at adecreased temperature, resulting in compounds of formula Ia.

Certain compounds of this invention are prepared from other compoundslisted in this invention via well-known functional grouptransformations. Such transformations include ester hydrolysis, amideformation, reductive alkylation, with examples of such described in thepreparations. Starting materials are prepared by known methods and aredescribed in the examples below.

Compounds included in this invention are exemplified by the followingexamples, which should not be construed as limiting the scope of thisdisclosure. Analogous structures and alternative mechanistic pathwayswithin the scope of the invention may be apparent to those skilled inthe art.

In the following examples, MH⁺ refers to the mass as determined by LC/MScarried out on a ThermoHypersil-Keystone BDS Hypersil C18 column (50mm×3 mm, 5 micron particle size). MNa⁺ is used to identify the productbased on its sodium adduct. Elution conditions for LC/MS are as follows:Solvents: A. Water with 0.05% TFA (v/v); B. Acetonitrile with 0.05% TFA(v/v); Flow rate: 3 mL/min Gradient Method Time (min) % B Conc 0 5 0.255 2.75 95 3.5 95 3.6 5 4.0 STOP

In isolating the following examples, it was necessary to employ a Varianreverse-phase preparative HPLC, utilizing a Phenomenex Aqua C₁₈ column(60 mm×21.2 mm, 5 micron particle size). Elution conditions for the HPLCare as follows: Solvents: A. Water with 0.05% TFA (v/v); B. Acetonitrilewith 0.05% TFA (v/v); Flow rate: 25 mL/min Gradient Method Time (min) %B Conc 0 5 0.75 5 9.5 100 10.5 100 11.5 5 12.0 STOP

EXAMPLE 1

Step 1:

A mixture of 3-phenylpropionaldehyde (215 mg; 1.6 mmol) andR-(−)-leucinol (187 mg; 1.6 mmol) in methanol was stirred at roomtemperature for 3 h. The reaction was treated with polystyrene boundborohydride (640 mg; 1.6 mmol) and stirred at room temperatureovernight. The final mixture was filtered, treated with polystyrenebound sulfonic acid (923 mg; 4.8 mmol) and stirred at room temperaturefor 1 h. The mixture was filtered, leaving the desired product isolatedon the resin. Subsequent treatment with 2.0M methanolic ammonia (8 ml)liberated the desired product, which was concentrated under nitrogenovernight.

Step 2

A mixture of the secondary amine from Step 1 (259 mg; 1.1 mmol) anddiisopropylethylamine (568 ul; 4.4 mmol) was stirred in CH₂Cl₂ at 0° C.for 1 h. A solution of 4-chlorobenzenesulfonylchloride (232 mg; 1.1mmol) in CH₂Cl₂ was added and subsequently stirred at 10° C. for 18 h.The crude reaction mixture was then purified on a Varian reverse-phasepreparative HPLC to afford the desired product.

EXAMPLE 2

Step 1

A mixture of R-(−)-2-benzylamino-1-butanol (36 mg; 0.2 mmol),4-chlorobenzenesulfonylchloride (51 mg; 0.24 mmol) and pyridine (126 ul;1.6 mmol) was stirred in CH₂Cl₂ at room temperature for 48 h. The crudereaction mixture was then purified on a Varian reverse-phase preparativeHPLC to afford the desired product.

The following compounds were prepared essentially according to themethods and procedures described above. EX. No. Name M + H+ M + Na+ 1N-benzyl-4-chloro-N-[(1S,2R)-2- 393.9(hydroxymethyl)cyclohexyl]benzenesulfonamide 24-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 438.1methyl-cyclohexyl)-benzenesulfonamide (one isomer) 34-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 438.1methyl-cyclohexyl)-benzenesulfonamide (second isomer) 44-Chloro-N-cyclooctyl-N-(3,4-dimethoxy- 474.1 benzyl)-benzenesulfonamide5 4-Chloro-N-(3,4-dimethoxy-benzyl)-N- 474.1(2,3-dimethyl-cyclohexyl)-benzenesulfonamide 64-Chloro-N-(3,4-dimethoxy-benzyl)-N-(4- 460.1methyl-cyclohexyl)-benzenesulfonamide 74-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 468.1phenyl-ethyl)-benzenesulfonamide 8 4-chloro-N-(3,4-dimethoxybenzyl)-N-498.1 [(1S,2R)-2-hydroxy-1-methyl-2- phenylethyl]benzenesulfonamide 94-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 450.0hydroxymethyl-2-methyl-propyl)- benzenesulfonamide 104-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 518.0naphthalen-1-yl-ethyl)-benzenesulfonamide 114-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 508.0phenyl-4,5-dihydro-1H-pyrazol-3-yl)- benzenesulfonamide 124-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3- 450.0hydroxy-2,2-dimethyl-propyl)- benzenesulfonamide 134-Chloro-N-(4-diethylamino-1-methyl- 483.2butyl)-N-(3,4-dimethoxy-benzyl)- benzenesulfonamide 144-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1- 546.0(4-methanesulfonyl-phenyl)-ethyl]- benzenesulfonamide 153-[(4-Chloro-benzenesulfonyl)-(3,4- 547.2dimethoxy-benzyl)-amino]-piperidine-1- carboxylic acid tert-butyl ester16 4-chloro-N-(3,4-dimethoxybenzyl)-N- 490.0 [(1S,3R,4R)-3-(hydroxymethyl)bicyclo[2.2.1]hept-2- yl]benzenesulfonamide 174-chloro-N-(3,4-dimethoxybenzyl)-N- 484.0 [(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide 18 N-[(1R)-1-benzyl-2-hydroxyethyl]-4-498.0 chloro-N-(3,4- dimethoxybenzyl)benzenesulfonamide 19N-[(4-chlorophenyl)sulfonyl]-N-(3,4- 511.1dimethoxybenzyl)-L-phenylalaninamide 204-chloro-N-(3,4-dimethoxybenzyl)-N- 514.1[(1R,2S)-2-hydroxy-1-(hydroxymethyl)-2- phenylethyl]benzenesulfonamide21 N-[(1S)-1-benzyl-2-hydroxyethyl]-4- 498.1 chloro-N-(3,4-dimethoxybenzyl)benzenesulfonamide 22 N-benzyl-4-chloro-N-[(1S,2S)-2-402.0 hydroxycyclohexyl]benzenesulfonamide 234-chloro-N-[(1R)-1-(hydroxymethyl)-3- 434.1 methylbutyl]-N-(4-methoxybenzyl)benzenesulfonamide 244-chloro-N-(4-chlorobenzyl)-N-[(1R)-1- 416.0 (hydroxymethyl)-3-methylbutyl]benzenesulfonamide 25 N-(4-bromobenzyl)-4-chloro-N-[(1R)-1-462.0 (hydroxymethyl)-3- methylbutyl]benzenesulfonamide 264-chloro-N-(2,4-difluorobenzyl)-N-[(1R)- 418.1 1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide 27 N-benzyl-4-chloro-N-[(1S)-1- 354.0(hydroxymethyl)propyl]benzenesulfonamide 284-chloro-N-[(1R)-1-(hydroxymethyl)-3- 410.1 methylbutyl]-N-(3-phenylpropyl)benzenesulfonamide 29N2-[(4-chlorophenyl)sulfonyl]-N1-methyl- 277.0 L-alaninamide 30N-tert-Butyl-2-(4-chloro- 347.0benzenesulfonylamino)-3-methyl-butyramide 314-Chloro-N-ethyl-N-[2-hydroxy-2-(3- 356.0hydroxy-phenyl)-ethyl]-benzenesulfonamide 324-Chloro-N-(2-hydroxy-1-methyl-2-phenyl- 362.0ethyl)-N-methyl-benzenesulfonamide 334-Chloro-N-methyl-N-(1-methyl-piperidin- 303.1 4-yl)-benzenesulfonamide34 4-Chloro-N-cyclohexyl-N-(2-hydroxy-2- 416.1phenyl-ethyl)-benzenesulfonamide 35 4-Chloro-N-ethyl-N-(2-pyridin-2-yl-325.1 ethyl)-benzenesulfonamide 36 N,N-Di-sec-butyl-4-chloro- 304.1benzenesulfonamide 37 4-Chloro-N-(2-cyano-ethyl)-N- 285.0cyclopropyl-benzenesulfonamide 38 4-Chloro-N-methyl-N-(2-pyridin-4-yl-311.1 ethyl)-benzenesulfonamide 39 [(4-Chloro-benzenesulfonyl)-methyl-292.0 amino]-acetic acid ethyl ester 404-chloro-N-[(1S,2S)-2-hydroxy-1-methyl- 362.02-phenylethyl]-N-methylbenzenesulfonamide 414-chloro-N-[(1R,2S)-2-hydroxy-1-methyl- 362.02-phenylethyl]-N-methylbenzenesulfonamide 424-Chloro-N-cyclohexyl-N-(2-hydroxy- 318.0 ethyl)-benzenesulfonamide 434-Chloro-N-cyanomethyl-N-methyl- 266.9 benzenesulfonamide 444-Chloro-N-(2-cyano-ethyl)-N-ethyl- 273.0 benzenesulfonamide 454-Chloro-N-isopropyl-N-(2-pyridin-4-yl- 339.0 ethyl)-benzenesulfonamide46 4-Chloro-N-[2-(3,4-dihydroxy-phenyl)-2- 356.0oxo-ethyl]-N-methyl-benzenesulfonamide 47 N-Allyl-4-chloro-N-cyclohexyl-314.0 benzenesulfonamide 48 4-Chloro-N,N-dicyclohexyl- 356.7benzenesulfonamide 49 4-Chloro-N-cyclohexyl-N-isopropyl- 315.8benzenesulfonamide 50 4-Chloro-N,N-diisopropyl- 275.5 benzenesulfonamide51 4-Chloro-N,N-divinyl-benzenesulfonamide 243.8 52N-(1-Benzyl-pyrrolidin-3-yl)-4-chloro-N- 379.0 ethyl-benzenesulfonamide53 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 508thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl- allyl)-benzenesulfonamide 544-Chloro-N-(2-hydroxy-propyl)-N-{3- 512methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide55 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 550.1thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-cyclohexyl)-benzenesulfonamide 564-Chloro-N-(2,3-dihydroxy-propyl)-N-{3- 528.9methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide57 4-Chloro-N-(1-hydroxymethyl-pentyl)-N- 554.1{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide 584-Chloro-N-cycloheptyl-N-{3-methoxy-4- 550[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 594-chloro-N-[(1S)-1-(hydroxymethyl)-3- 554methylbutyl]-N-{3-methoxy-4-[2-(4-methyl-1,3- thiazol-5-yl)ethoxy]benzyl}benzenesulfonamide 60 N-(2-Amino-benzyl)-4-chloro-N-{3-559 methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide 61 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 542thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methylsulfanyl-propyl)-benzenesulfonamide 624-Chloro-N-(3-hydroxy-butyl)-N-{3- 526methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide63 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 544.9thiazol-5-yl)-ethoxy]-benzyl}-N-pyridin-2- ylmethyl-benzenesulfonamide64 4-Chloro-N-(2,4-dichloro-benzyl)-N-{3- 612.9methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide65 4-chloro-N-{[(1R,2S)-2- 566hydroxycyclohexyl]methyl}-N-{3-methoxy-4-[2- (4-methyl-1,3-thiazol-5-yl) ethoxy]benzyl}benzenesulfonamide 664-Chloro-N-cyclohexyl-N-{3-methoxy-4-[2- 535.8(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 674-Chloro-N-{3-methoxy-4-[2-(4-methyl- 549.8thiazol-5-yl)-ethoxy]-benzyl}-N-(4-methyl-cyclohexyl)-benzenesulfonamide 684-Chloro-N-cyclobutyl-N-{3-methoxy-4-[2- 507.8(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 694-Chloro-N-cyclopentyl-N-{3-methoxy-4- 521.8[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 704-Chloro-N-{3-methoxy-4-[2-(4-methyl- 525.8thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methoxy- propyl)-benzenesulfonamide71 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 491.8thiazol-5-yl)-ethoxy]-benzyl}-N-prop-2-ynyl- benzenesulfonamide 724-Chloro-N-{3-methoxy-4-[2-(4-methyl- 537.8thiazol-5-yl)-ethoxy]-benzyl}-N-(tetrahydro-furan-2-ylmethyl)-benzenesulfonamide 734-Chloro-N-cyclopropylmethyl-N-{3- 507.8methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide74 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 523.8thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl- butyl)-benzenesulfonamide 754-Chloro-N-{3-methoxy-4-[2-(4-methyl- 557.9thiazol-5-yl)-ethoxy]-benzyl}-N-(1-phenyl- ethyl)-benzenesulfonamide 764-Chloro-N-{3-methoxy-4-[2-(4-methyl- 523.8thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methyl- butyl)-benzenesulfonamide 774-Chloro-N-ethyl-N-{3-methoxy-4-[2-(4- 481.8methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 784-chloro-N-(3,4-dimethoxybenzyl)-N- 437 [(1S)-1-(hydroxymethyl)propyl]benzenesulfonamide 794-chloro-N-(3,4-dimethoxybenzyl)-N- 465.1 [(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide 804-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 475.1methyl-cyclohexyl)-benzenesulfonamide 81 N-Benzyl-N-sec-butyl-4-chloro-361 benzenesulfonamide 82 4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 438.8methyl-cyclohexyl)-benzenesulfonamide 834-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 438.8methyl-cyclohexyl)-benzenesulfonamide 84N-(1,3-benzodioxol-5-ylmethyl)-4-chloro- 449.1N-[(1S)-1-(hydroxymethyl)-3- methylbutyl]benzenesulfonamide 854-chloro-N-(2,3-dihydro-1,4-benzodioxin- 463.16-ylmethyl)-N-[(1S)-1-(hydroxymethyl)-3- methylbutyl]benzenesulfonamide86 4-chloro-N-(3,4-dimethylbenzyl)-N-[(1S)- 433.1 1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide 874-chloro-N-(3-fluoro-4-methoxybenzyl)-N- 453.1[(1S)-1-(hydroxymethyl)-3- methylbutyl]benzenesulfonamide 884-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 461.1methyl-cyclohexyl)-benzenesulfonamide 894-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 461.1methyl-cyclohexyl)-benzenesulfonamide 904-chloro-N-[(1S)-1-(hydroxymethyl)-3- 431.1methylbutyl]-N-[(2E)-3-phenylprop-2-en-1- yl]benzenesulfonamide 914-chloro-N-[(1S)-1-(hydroxymethyl)-3- 445.1methylbutyl]-N-[(2E)-2-methyl-3-phenylprop-2- en-1-yl]benzenesulfonamide92 4-Chloro-N-(1-hydroxymethyl-3-methyl- 444butyl)-N-(1-methyl-3-phenyl-allyl)- benzenesulfonamide 93N-(2-Benzyl-cyclohexyl)-4-chloro-N-(1- 486.2hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 944-Chloro-N-(1-hydroxymethyl-3-methyl- 444butyl)-N-(1,2,3,4-tetrahydro-naphthalen-2- yl)-benzenesulfonamide 954-Chloro-N-(4,6-dichloro-2H-chromen-3- 527ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 964-Chloro-N-(1-hydroxymethyl-3-methyl- 435.1butyl)-N-(1-methyl-1H-indol-2-ylmethyl)- benzenesulfonamide 974-Chloro-N-(1-chloro-3,4-dihydro- 490.1naphthalen-2-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 984-Chloro-N-(1-hydroxymethyl-3-methyl- 424.1butyl)-N-(1-methyl-3-phenyl-propyl)- benzenesulfonamide 994-Chloro-N-(1-hydroxymethyl-3-methyl- 334butyl)-N-propyl-benzenesulfonamide 1004-Chloro-N-(1-hydroxymethyl-3-methyl- 306.1butyl)-N-methyl-benzenesulfonamide 101N-sec-Butyl-4-chloro-N-(4-chloro-6- 466 fluoro-2H-chromen-3-ylmethyl)-benzenesulfonamide 102 N-sec-Butyl-4-chloro-N-(4,6-dichloro-2H- 460chromen-3-ylmethyl)-benzenesulfonamide 103N-sec-Butyl-4-chloro-N-(2-pentyl-3- 456.1phenyl-allyl)-benzenesulfonamide 104N-sec-Butyl-4-chloro-N-(3,3-diphenyl- 462.1 allyl)-benzenesulfonamide105 N-Benzofuran-2-ylmethyl-N-sec-butyl-4- 400 chloro-benzenesulfonamide106 N-sec-Butyl-4-chloro-N-(1-methyl-1H- 391.1indol-2-ylmethyl)-benzenesulfonamide 107N-sec-Butyl-4-chloro-N-(1-chloro-3,4- 445.9dihydro-naphthalen-2-ylmethyl)- benzenesulfonamide 1084-Chloro-N-(1-hydroxymethyl-3-methyl- 460.1butyl)-N-[3-(2-methoxy-phenyl)-allyl]- benzenesulfonamide 109N-Benzofuran-2-ylmethyl-4-chloro-N-(1- 444.0hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 1104-Chloro-N-cyclopropylmethyl-N-(1- 346.0 hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 111 4-Chloro-N-(2-methyl-cyclohexyl)-N-(3- 426.1phenyl-allyl)-benzenesulfonamide 1124-Chloro-N-(1-hydroxymethyl-3-methyl- 424.1butyl)-N-(3-phenyl-butyl)-benzenesulfonamide 1134-Chloro-N-(1-methyl-butyl)-N-(3-phenyl- 400.1 allyl)-benzenesulfonamide114 4-Chloro-N-(1,3-dimethyl-butyl)-N-(3- 414.1phenyl-allyl)-benzenesulfonamide 1154-Chloro-N-(2-methyl-cyclohexyl)-N-(3- 428.1phenyl-propyl)-benzenesulfonamide 1164-Chloro-N-(1-methyl-butyl)-N-(3-phenyl- 380.1propyl)-benzenesulfonamide 117 4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-400.1 allyl)-benzenesulfonamide 118 N-[3-(4-tert-Butyl-phenyl)-2-methyl-480.2 propyl]-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 119 4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-394.1 phenyl-propyl)-benzenesulfonamide 1204-Chloro-N-(2-methoxy-1-methyl-ethyl)-N- 382.1(3-phenyl-propyl)-benzenesulfonamide 1214-Chloro-N-(4-chloro-6-fluoro-2H- 510.1chromen-3-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 1224-Chloro-N-(2-methoxy-1-methyl-ethyl)-N- 402.0(3-phenyl-allyl)-benzenesulfonamide 1234-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl- 380.0propyl)-benzenesulfonamide 124 4-Chloro-N-(1,2-dimethyl-propyl)-N-(3-400.1 phenyl-allyl)-benzenesulfonamide 125N-sec-Butyl-4-chloro-N-(1-methyl-3- 402.1phenyl-propyl)-benzenesulfonamide 126N-sec-Butyl-4-chloro-N-(3-phenyl-allyl)- 386.0 benzenesulfonamide 1274-Chloro-N-(1-hydroxymethyl-propyl)-N- 382.1(3-phenyl-propyl)-benzenesulfonamide 1284-Chloro-N-(2-hydroxy-propyl)-N-(3- 368.1phenyl-propyl)-benzenesulfonamide 1294-Chloro-N-(1-hydroxymethyl-propyl)-N- 402.0(3-phenyl-allyl)-benzenesulfonamide 1304-Chloro-N-(1,2-dimethyl-propyl)-N-(3- 380.1phenyl-propyl)-benzenesulfonamide 131N-sec-Butyl-4-chloro-N-[3-(2-methoxy- 416.1phenyl)-allyl]-benzenesulfonamide 1324-Chloro-N-(2-hydroxy-propyl)-N-(3- 388.0phenyl-allyl)-benzenesulfonamide 133 N-sec-Butyl-4-chloro-N-(3-phenyl-366.1 propyl)-benzenesulfonamide 134 N-sec-Butyl-4-chloro-N-(1-methyl-3-400.1 phenyl-allyl)-benzenesulfonamide 1352-[(4-Chloro-benzenesulfonyl)-(3-phenyl- 426.1propyl)-amino]-3-hydroxy-N-methyl-butyramide 1364-Chloro-N-(1-hydroxymethyl-3-methyl- 500.1butyl)-N-(2-pentyl-3-phenyl-allyl)- benzenesulfonamide 137N-sec-Butyl-4-chloro-N-(3-phenyl-butyl)- 380.1 benzenesulfonamide 138(S)-4-chloro-N-cinnamyl-N-(1-hydroxy-4- 431.1methylpentan-2-yl)benzenesulfonamide 1394-Chloro-N-(1-hydroxymethyl-3-methyl- 410.1butyl)-N-(3-phenyl-propyl)-benzenesulfonamide 1404-Chloro-N-(1-hydroxymethyl-3-methyl- 445.1butyl)-N-(2-methyl-3-phenyl-allyl)- benzenesulfonamide 1414-Chloro-N-(2,3-dihydro-benzo[1,4]dioxin- 463.16-ylmethyl)-N-(1-hydroxymethyl-3-methyl- butyl)-benzenesulfonamide 142N-Benzo[1,3]dioxol-5-ylmethyl-4-chloro-N- 449.1(1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 1434-Chloro-N-(3-fluoro-4-methoxy-benzyl)-N- 453.1(1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 1444-Chloro-N-(2,4-difluoro-benzyl)-N-(1- 418.1 —hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 1454-Chloro-N-(1-hydroxymethyl-3-methyl- 434.1butyl)-N-(4-methoxy-benzyl)-benzenesulfonamide 1464-Chloro-N-(4-chloro-benzyl)-N-(1- 416.0 —hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 147N-(4-Bromo-benzyl)-4-chloro-N-(1- 462.0 — hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 148 4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 438.1 —methyl-cyclohexyl)-benzenesulfonamide 1494-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 438.8methyl-cyclohexyl)-benzenesulfonamide 150N-Benzyl-4-chloro-N-(1-hydroxymethyl- 354.0 — propyl)-benzenesulfonamide151 4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 475.1methyl-cyclohexyl)-benzenesulfonamide 1524-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 465.1hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 153N-Benzyl-4-chloro-N-(2-hydroxy- 402.0 cyclohexyl)-benzenesulfonamide 154N,N-Di-sec-butyl-4-chloro- 304.1 — benzenesulfonamide 1554-Chloro-N-(1-hydroxymethyl-3-methyl- 554butyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide 1564-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 461.1methyl-cyclohexyl)-benzenesulfonamide 1574-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 450.0hydroxymethyl-2-methyl-propyl)- benzenesulfonamide 1584-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 437hydroxymethyl-propyl)-benzenesulfonamide 1594-Chloro-N-cyclohexyl-N-isopropyl- 315.8 benzenesulfonamide 1604-Chloro-N-{3-methoxy-4-[2-(4-methyl- 550.1thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-cyclohexyl)-benzenesulfonamide 1614-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 461.1methyl-cyclohexyl)-benzenesulfonamide 162 4-Chloro-N,N-diisopropyl-275.5 — benzenesulfonamide 163 4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-438.1 — methyl-cyclohexyl)-benzenesulfonamide 1644-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 438.8methyl-cyclohexyl)-benzenesulfonamide 1654-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,3- 474.1dimethyl-cyclohexyl)-benzenesulfonamide 166N-Benzyl-N-sec-butyl-4-chloro- 361 benzenesulfonamide 1674-Chloro-N-(1-hydroxymethyl-pentyl)-N-{3- 554.1methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide168 4-Chloro-N-cyclooctyl-N-(3,4-dimethoxy- 474.1benzyl)-benzenesulfonamide 169 4-Chloro-N-cyclohexyl-N-{3-methoxy-4-[2-535.8 (4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 170N-Allyl-4-chloro-N-cyclohexyl- 314.0 — benzenesulfonamide 1714-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 484.0hydroxy-1-phenyl-ethyl)-benzenesulfonamide 1724-Chloro-N-(3,4-dimethoxy-benzyl)-N-(4- 460.1methyl-cyclohexyl)-benzenesulfonamide 1734-Chloro-N-(3-hydroxy-butyl)-N-{3-methoxy- 5264-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 1744-Chloro-N-(2-hydroxy-cyclohexylmethyl)-N- 566{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide 1754-Chloro-N,N-divinyl-benzenesulfonamide 243.8 — 1764-Chloro-N,N-dicyclohexyl- 356.7 — benzenesulfonamide 1774-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3- 450.0hydroxy-2,2-dimethyl-propyl)- benzenesulfonamide 1784-Chloro-N-cyclopentyl-N-{3-methoxy-4-[2- 521.8(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 179N-(2-Amino-benzyl)-4-chloro-N-{3-methoxy- 5594-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 1804-Chloro-N-cyclohexyl-N-(2-hydroxy-2- — 416.1phenyl-ethyl)-benzenesulfonamide 1814-Chloro-N-{3-methoxy-4-[2-(4-methyl- 523.8thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl- butyl)-benzenesulfonamide 1824-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3- 490.0hydroxymethyl-bicyclo[2.2.1]hept-2-yl)- benzenesulfonamide 1834-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 498.0hydroxymethyl-2-phenyl-ethyl)- benzenesulfonamide 1844-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1-(4- 546.0methanesulfonyl-phenyl)-ethyl]- benzenesulfonamide 1854-Chloro-N-(2-hydroxy-propyl)-N-{3- 512methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide186 3-[(4-Chloro-benzenesulfonyl)-(3,4- 547.2dimethoxy-benzyl)-amino]-piperidine-1- carboxylic acid tert-butyl ester187 4-Chloro-N-cycloheptyl-N-{3-methoxy-4-[2- 550(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 1884-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 468.1phenyl-ethyl)-benzenesulfonamide 1894-Chloro-N-{3-methoxy-4-[2-(4-methyl- 542thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methylsulfanyl-propyl)-benzenesulfonamide 1904-Chloro-N-{3-methoxy-4-[2-(4-methyl- 549.8thiazol-5-yl)-ethoxy]-benzyl}-N-(4-methyl-cyclohexyl)-benzenesulfonamide 1914-Chloro-N-ethyl-N-{3-methoxy-4-[2-(4- 481.8methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 1924-Chloro-N-{3-methoxy-4-[2-(4-methyl- 544.9thiazol-5-yl)-ethoxy]-benzyl}-N-pyridin-2- ylmethyl-benzenesulfonamide193 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 491.8thiazol-5-yl)-ethoxy]-benzyl}-N-prop-2-ynyl- benzenesulfonamide 1944-Chloro-N-{3-methoxy-4-[2-(4-methyl- 523.8thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methyl- butyl)-benzenesulfonamide 1954-Chloro-N-{3-methoxy-4-[2-(4-methyl- 537.8thiazol-5-yl)-ethoxy]-benzyl}-N-(tetrahydro-furan-2-ylmethyl)-benzenesulfonamide 1964-Chloro-N-cyclopropylmethyl-N-{3-methoxy- 507.84-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 1974-Chloro-N-{3-methoxy-4-[2-(4-methyl- 525.8thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methoxy- propyl)-benzenesulfonamide198 4-Chloro-N-(2,4-dichloro-benzyl)-N-{3- 612.9methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide199 4-Chloro-N-(2,3-dihydroxy-propyl)-N-{3- 528.9methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]- benzyl}-benzenesulfonamide200 4-Chloro-N-isopropyl-N-(2-pyridin-4-yl- 339.0 —ethyl)-benzenesulfonamide 201 4-Chloro-N-cyclobutyl-N-{3-methoxy-4-[2-507.8 (4-methyl-thiazol-5-yl)-ethoxy]-benzyl}- benzenesulfonamide 2024-Chloro-N-cyclohexyl-N-(2-hydroxy-ethyl)- 318.0 — benzenesulfonamide203 N-Benzyl-4-chloro-N-(2-hydroxymethyl- 393.9 —cyclohexyl)-benzenesulfonamide 2044-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 498.1hydroxy-1-methyl-2-phenyl-ethyl)- benzenesulfonamide 2054-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 518.0naphthalen-1-yl-ethyl)-benzenesulfonamide 2064-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- 508.0phenyl-4,5-dihydro-1H-pyrazol-3-yl)- benzenesulfonamide 2074-Chloro-N-(4-diethylamino-1-methyl- 483.2 —butyl)-N-(3,4-dimethoxy-benzyl)- benzenesulfonamide 2082-[(4-Chloro-benzenesulfonyl)-(3,4- 511.1dimethoxy-benzyl)-amino]-3-phenyl-propionamide 2094-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2- 514.1hydroxy-1-hydroxymethyl-2-phenyl-ethyl)- benzenesulfonamide 2104-Ghloro-N-(3,4-dimethoxy-benzyl)-N-(1- 498.1hydroxymethyl-2-phenyl-ethyl)- benzenesulfonamide 2112-(4-Chloro-benzenesulfonylamino)-N- 277.0 methyl-propionamide 212N-tert-Butyl-2-(4-chloro- 347.0benzenesulfonylamino)-3-methyl-butyramide 2134-Chloro-N-ethyl-N-[2-hydroxy-2-(3- 356.0hydroxy-phenyl)-ethyl]-benzenesulfonamide 2144-Chloro-N-(2-hydroxy-1-methyl-2-phenyl- 362.0ethyl)-N-methyl-benzenesulfonamide 2154-Chloro-N-methyl-N-(1-methyl-piperidin-4- 303.1 yl)-benzenesulfonamide216 4-Chloro-N-ethyl-N-(2-pyridin-2-yl-ethyl)- 325.1 benzenesulfonamide217 4-Chloro-N-(2-cyano-ethyl)-N-cyclopropyl- 285.0 benzenesulfonamide218 4-Chloro-N-methyl-N-(2-pyridin-4-yl- 311.1 ethyl)-benzenesulfonamide219 [(4-Chloro-benzenesulfonyl)-methyl-amino]- 292.0 acetic acid ethylester 220 4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl- 362.0ethyl)-N-methyl-benzenesulfonamide 2214-Chloro-N-(2-hydroxy-1-methyl-2-phenyl- 362.0ethyl)-N-methyl-benzenesulfonamide 222 4-Chloro-N-cyanomethyl-N-methyl-266.9 benzenesulfonamide 223 4-Chloro-N-(2-cyano-ethyl)-N-ethyl- 273.0benzenesulfonamide 224 4-Chloro-N-[2-(3,4-dihydroxy-phenyl)-2- 356.0oxo-ethyl]-N-methyl-benzenesulfonamide 225N-(1-Benzyl-pyrrolidin-3-yl)-4-chloro-N- 379.0 ethyl-benzenesulfonamide226 4-Chloro-N-{3-methoxy-4-[2-(4-methyl- 557.9thiazol-5-yl)-ethoxy]-benzyl}-N-(1-phenyl- ethyl)-benzenesulfonamide 2274-Chloro-N-{3-methoxy-4-[2-(4-methyl- 508thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl- allyl)-benzenesulfonamide 228[2-(4-Chloro-benzenesulfonylimino)- 318.0 imidazolidin-1-yl]-acetic acid229 4-Chloro-N-pyrrolidin-3-yl- 261.0 benzenesulfonamide 2304-Chloro-N-(2-chloro-3-phenyl-allyl)-N- — 464(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2314-Chloro-N-[3-(3-fluoro-phenyl)-allyl]- — 447.9N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2324-Chloro-N-(R-1-hydroxymethyl-3-methyl- 410.1 —butyl)-N-(3-phenyl-propyl)-benzenesulfonamide 2334-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 431butyl)-N-(3-phenyl-allyl)-benzenesulfonamide 2344-Chloro-N-(2,3-dihydro- — 463 benzo[1,4]dioxin-6-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 235N-Benzofuran-2-ylmethyl-4-chloro-N-(R-1- — 444hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2364-[(4-Chloro-benzenesulfonyl)-(R-1- — 440hydroxymethyl-3-methyl-butyl)-amino]-3- methyl-but-2-enoic acid ethylester 237 4-Chloro-N-(R-1-hydroxymethyl-3-methyl- 409 —butyl)-N-(3-pyridin-3-yl-allyl)- benzenesulfonamide 2384-Chloro-N-cyclohexylmethyl-N-(R-1- 388 — hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 239 4-Chloro-N-[3-(2-fluoro-phenyl)-allyl]- — 447.9N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 240N-(2-Bromo-3-phenyl-allyl)-4-chloro-N- — 509.9(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 241N-Benzo[1,3]dioxol-5-ylmethyl-4-chloro- — 449N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2424-Chloro-N-(3-fluoro-4-methoxy-benzyl)- — 453N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2434-Chloro-N-[3-(3-chloro-phenyl)-allyl]- — 463.9N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2444-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 445butyl)-N-(2-methyl-3-phenyl-allyl)- benzenesulfonamide 2454-Chloro-N-(2,4-difluoro-benzyl)-N-(R-1- 418.1 —hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2464-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 434.1butyl)-N-(4-methoxy-benzyl)- benzenesulfonamide 2474-Chloro-N-(4-chloro-benzyl)-N-(R-1- 416 —hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 248N-(4-Bromo-benzyl)-4-chloro-N-(R-1- — 483.1hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2494-Chloro-N-[3-(4-fluoro-phenyl)-allyl]- — 447.9N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2504-Chloro-N-(R-1-hydroxymethyl-3-methyl- 455 —butyl)-N-[3-(2-nitro-phenyl)-allyl]- benzenesulfonamide 2514-Chloro-N-(2-methyl-cyclohexyl)-N-(3- 406 —pyridin-3-yl-allyl)-benzenesulfonamide 252N-(6-Bromo-pyridin-3-ylmethyl)-4-chloro- 459 —N-(2-methyl-cyclohexyl)-benzenesulfonamide 2534-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 444butyl)-N-(3-m-tolyl-allyl)-benzenesulfonamide 2544-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 444butyl)-N-(3-o-tolyl-allyl)-benzenesulfonamide 2554-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 460.1butyl)-N-[3-(2-methoxy-phenyl)-allyl]- benzenesulfonamide 2564-Chloro-N-(6-chloro-pyridin-3- 414 — ylmethyl)-N-(2-methyl-cyclohexyl)-benzenesulfonamide 257 4-Chloro-N-(6-methoxy-pyridin-3- 410 —ylmethyl)-N-(2-methyl-cyclohexyl)- benzenesulfonamide 2584-Chloro-N-cyclopropylmethyl-N-(R-1- 346 —hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2594-Chloro-N-(R-1-hydroxymethyl-3-methyl- 334 —butyl)-N-propyl-benzenesulfonamide 2604-Chloro-N-furan-3-ylmethyl-N-(R-1- — 393.9hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2614-Chloro-N-(R-1-hydroxymethyl-3-methyl- 362 —butyl)-N-pentyl-benzenesulfonamide 2624-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 454butyl)-N-naphthalen-2-ylmethyl- benzenesulfonamide 2634-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 446butyl)-N-(1-methyl-3-phenyl-propyl)- benzenesulfonamide 2644-Chloro-N-(2-ethyl-allyl)-N-(R-1- 360 — hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 265 N-(4-Bromo-benzyl)-4-chloro-N-(2,5- — 494dimethyl-cyclohexyl)-benzenesulfonamide 2664-Chloro-N-furan-2-ylmethyl-N-(R-1- — 393.9hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 267N-Benzyl-4-chloro-N-(1S,2S-2-hydroxy- — 402cyclohexyl)-benzenesulfonamide 2684-Chloro-N-(2-methyl-cyclohexyl)-N-(3- — 426.1phenyl-allyl)-benzenesulfonamide 269 4-Chloro-N-(3-furan-2-yl-2-methyl-412 — allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide270 4-Chloro-N-(3,4-dimethoxy-benzyl)-N- — 475(2,5-dimethyl-cyclohexyl)-benzenesulfonamide 2714-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 444butyl)-N-(3-p-tolyl-allyl)-benzenesulfonamide 2724-Chloro-N-(2,5-dimethyl-cyclohexyl)-N- — 445(4-methoxy-benzyl)-benzenesulfonamide 2734-Chloro-N-[3-(4-chloro-phenyl)-allyl]- — 464N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 2744-Chloro-N-(R-1-hydroxymethyl-3-methyl- 424.1 —butyl)-N-(3-phenyl-butyl)-benzenesulfonamide 2754-Chloro-N-(2,5-dimethyl-cyclohexyl)-N- — 463(3-fluoro-4-methoxy-benzyl)- benzenesulfonamide 2764-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- — 450hydroxymethyl-2-methyl-propyl)- benzenesulfonamide 2774-Chloro-N-(1-methyl-butyl)-N-(3-phenyl- — 400.1allyl)-benzenesulfonamide 278 4-Chloro-N-(1,3-dimethyl-butyl)-N-(3- —414.1 phenyl-allyl)-benzenesulfonamide 2794-Chloro-N-(R-1-hydroxymethyl-3-methyl- 376 —butyl)-N-(2-methyl-pentyl)-benzenesulfonamide 2804-Chloro-N-(2,5-dimethyl-cyclohexyl)-N- — 455(2-methyl-3-phenyl-allyl)-benzenesulfonamide 2814-[(4-Chloro-benzenesulfonyl)-(R-1- 404 —hydroxymethyl-3-methyl-butyl)-amino]-but-2- enoic acid ethyl ester 2824-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 444butyl)-N-(1-methyl-3-phenyl-allyl)- benzenesulfonamide 2834-Chloro-N-(1-chloro-3,4-dihydro- — 490naphthalen-2-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 2844-Chloro-N-(R-1-hydroxymethyl-3-methyl- 452.1 —butyl)-N-(2-methyl-4-phenyl-pentyl)- benzenesulfonamide 2854-Chloro-N-(2,4-difluoro-benzyl)-N-(2,5- — 451dimethyl-cyclohexyl)-benzenesulfonamide 2874-Chloro-N-(2-methyl-cyclohexyl)-N-(3- — 428.1phenyl-propyl)-benzenesulfonamide 2884-Chloro-N-(1-methyl-butyl)-N-(3-phenyl- 380.1 —propyl)-benzenesulfonamide 289 4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-— 400.1 allyl)-benzenesulfonamide 2904-Chloro-N-(2,5-dimethyl-cyclohexyl)-N- — 441(3-phenyl-allyl)-benzenesulfonamide 2914-Chloro-N-[3-(4-dimethylamino-phenyl)- 451 —allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 292N-[3-(4-tert-Butyl-phenyl)-2-methyl- 480.2 —propyl]-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 2934-Chloro-N-(1,3-dimethyl-butyl)-N-(3- 394.1 —phenyl-propyl)-benzenesulfonamide 2944-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 382butyl)-N-(3-methyl-but-2-enyl)- benzenesulfonamide 2954-Chloro-N-(R-1-hydroxymethyl-3-methyl- 362 —butyl)-N-(3-methyl-butyl)-benzenesulfonamide 2964-Chloro-N-(3,4-dimethoxy-benzyl)-N- — 474.1(2,3-dimethyl-cyclohexyl)-benzenesulfonamide 2974-Chloro-N-(4,6-dichloro-2H-chromen-3- — 526.9ylmethyl)-N-(R-1-hydroxymethyl-3-methyl- butyl)-benzenesulfonamide 2984-Chloro-N-(2,5-dimethyl-cyclohexyl)-N- — 443(3-phenyl-propyl)-benzenesulfonamide 299 N-But-2-enyl-4-chloro-N-(R-1-346 — hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 3004-Chloro-N-(S-1,2-dimethyl-propyl)-N-(3- — 400phenyl-allyl)-benzenesulfonamide 3014-Chloro-N-(R-1-hydroxymethyl-3-methyl- 306.1 —butyl)-N-methyl-benzenesulfonamide 3024-Chloro-N-cyclooctyl-N-(3,4-dimethoxy- — 474.1benzyl)-benzenesulfonamide 303 4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-— 402 (3-phenyl-allyl)-benzenesulfonamide 3044-Chloro-N-(2-methoxy-1-methyl-ethyl)-N- 382.1 —(3-phenyl-propyl)-benzenesulfonamide 3054-Chloro-N-(4-chloro-6-fluoro-2H- — 510.1chromen-3-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide 3064-Chloro-N-(R-1-hydroxymethyl-3-methyl- 435 —butyl)-N-(1-methyl-1H-indol-2-ylmethyl)- benzenesulfonamide 3074-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl- 380.1 —propyl)-benzenesulfonamide 308 4-Chloro-N-(R-1-hydroxymethyl-3-methyl- —444 butyl)-N-(1,2,3,4-tetrahydro-naphthalen-2- yl)-benzenesulfonamide309 4-Chloro-N-(R-1,2-dimethyl-propyl)-N-(3- — 400.1phenyl-allyl)-benzenesulfonamide 310 4-Chloro-N-(2-ethyl-butyl)-N-(R-1-376 — hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 3114-Chloro-N-(3,4-dimethoxy-benzyl)-N-(R- — 4842-hydroxy-1-phenyl-ethyl)-benzenesulfonamide 312R-N-sec-Butyl-4-chloro-N-(1-methyl-3- — 402.1phenyl-propyl)-benzenesulfonamide 313R-N-sec-Butyl-4-chloro-N-(3-phenyl- — 386 allyl)-benzenesulfonamide 314R-N-Benzofuran-2-ylmethyl-N-sec-butyl-4- — 400 chloro-benzenesulfonamide315 4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(4- — 460.1methyl-cyclohexyl)-benzenesulfonamide 3164-Chloro-N-(1-hydroxymethyl-propyl)-N- 382.1 —(3-phenyl-propyl)-benzenesulfonamide 317N-(2-Benzyl-cyclohexyl)-4-chloro-N-(R-1- — 486.2hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 3184-Chloro-N-(2-hydroxy-propyl)-N-(3- 368 —phenyl-propyl)-benzenesulfonamide 3194-Chloro-N-(1-hydroxymethyl-propyl)-N- — 402(3-phenyl-allyl)-benzenesulfonamide 3204-Chloro-N-(R-1,2-dimethyl-propyl)-N-(3- 380.1 —phenyl-propyl)-benzenesulfonamide 321R-N-sec-Butyl-4-chloro-N-[3-(2-methoxy- — 416.1phenyl)-allyl]-benzenesulfonamide 3224-Chloro-N-(3-furan-2-yl-allyl)-N-(R-1- — 419.9hydroxymethyl-3-methyl-butyl)- benzenesulfonamide 3234-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3- — 450hydroxy-2,2-dimethyl-propyl)- benzenesulfonamide 3244-Chloro-N-(2-hydroxy-propyl)-N-(3- — 388phenyl-allyl)-benzenesulfonamide 325 R-N-sec-Butyl-4-chloro-N-(3-phenyl-— 388.1 propyl)-benzenesulfonamide 326R-N-sec-Butyl-4-chloro-N-(1-methyl-1H- 391.1 —indol-2-ylmethyl)-benzenesulfonamide 328R-N-sec-Butyl-4-chloro-N-(1-methyl-3- — 400.1phenyl-allyl)-benzenesulfonamide 3292S,3R-2-[(4-Chloro-benzenesulfonyl)-(3- 426.1 —phenyl-propyl)-amino]-3-hydroxy-N-methyl- butyramide 3304-Chloro-N-(R-1-hydroxymethyl-3-methyl- — 500.1butyl)-N-(2-pentyl-3-phenyl-allyl)- benzenesulfonamide 3314-Chloro-N-(3,4-dimethoxy-benzyl)-N- — 503(1R,2S,5R-2-isopropyl-5-methyl-cyclohexyl)- benzenesulfonamide 332R-N-sec-Butyl-4-chloro-N-(1-chloro-3,4- — 446.9dihydro-naphthalen-2-ylmethyl)- benzenesulfonamide 3333-[(4-Chloro-benzenesulfonyl)-(3-phenyl- — 513.1allyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester 3344-[(4-Chloro-benzenesulfonyl)-(3-phenyl- — 485.1allyl)-amino]-piperidine-1-carboxylic acid ethyl ester 3354-Chloro-N-(1S,2S-2-hydroxy- 394.1 — cyclopentyl)-N-(3-phenyl-propyl)-benzenesulfonamide 336 4-[(4-Chloro-benzenesulfonyl)-(3-phenyl- 465.1 —propyl)-amino]-piperidine-1-carboxylic acid ethyl ester 3374-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3- — 490hydroxymethyl-bicyclo[2.2.1]hept-2-yl)- benzenesulfonamide 3384-Chloro-N-(S-1-hydroxymethyl-3-methyl- 292 — butyl)-benzenesulfonamide339 4-Chloro-N-(R-1-hydroxymethyl-3-methyl- 292 —butyl)-benzenesulfonamide 340 4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(R- —498 1-hydroxymethyl-2-phenyl-ethyl)- benzenesulfonamide 3414-Chloro-N-(S-1-hydroxymethyl-3-methyl- — 430butyl)-N-(3-phenyl-allyl)-benzenesulfonamide 3424-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1- 524 —(4-methanesulfonyl-phenyl)-ethyl]- benzenesulfonamide 3433-[(4-Chloro-benzenesulfonyl)-(3,4- — 547.2dimethoxy-benzyl)-amino]-piperidine-1- carboxylic acid tert-butyl ester344 4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1- — 468.1phenyl-ethyl)-benzenesulfonamide 345 4-Chloro-N-(R-1,2-dimethyl-propyl)-262 — benzenesulfonamideNotch Signaling Assay for Selective Inhibitors of Gamma Secretase

A convergence of evidence indicates that the gamma secretase complex,comprised of the presenilin subunits, mediates the intra-membranecleavage of Amyloid precursor protein (APP), and the Notch family ofproteins (De Strooper, B., P. Saftig, K. Craessaerts, H. Vanderstichele,G. Guhde, W. Annaert, K. Von Figura and F. Van Leuven (1998).“Deficiency of presenilin-1 inhibits the normal cleavage of amyloidprecursor protein.” Nature 391(6665): 387-90; De Strooper, B., W.Annaert, P. Cupers, P. Saftig, K. Craessaerts, J. S. Mumm, E. H.Schroeter, V. Schrijvers, M. S. Wolfe, W. J. Ray et al. (1999). “Apresenilin-1-dependent gamma-secretase-like protease mediates release ofNotch intracellular domain.” Nature 398(6727): 518-22; Mumm, J. S., E.H. Schroeter, M. T. Saxena, A. Griesemer, X. Tian, D. J. Pan, W. J. Rayand R. Kopan (2000). “A ligand-induced extracellular cleavage regulatesgamma-secretase-like proteolytic activation of Notch1.” Mol Cell 5(2):197-206; Zhang, Z., P. Nadeau, W. Song, D. Donoviel, M. Yuan, A.Bernstein and B. A. Yankner (2000). “Presenilins are required forgamma-secretase cleavage of beta-APP and transmembrane cleavage ofNotch-1.” Nat Cell Biol 2(7): 463-5). Cleavage of APP by gamma secretaseleads to β-amyloid synthesis. Cleavage of Notchl by gamma secretaseresults in release of the Notch intracellular domain (NICD), whichtranslocates to the nucleus and activates gene expression (Jarriault,S., C. Brou, F. Logeat, E. H. Schroeter, R. Kopan and A. Israel (1995).“Signalling downstream of activated mammalian Notch.” Nature 377(6547):355-8; Kopan, R., E. H. Schroeter, H. Weintraub and J. S. Nye (1996).“Signal transduction by activated Notch: importance of proteolyticprocessing and its regulation by the extracellular domain.” Proc NatlAcad Sci U S A 93(4): 1683-8; Schroeter, E. H., J. A. Kisslinger and R.Kopan (1998). “Notch-1 signalling requires ligand-induced proteolyticrelease of intracellular domain.” Nature 393(6683): 382-6). Inparticular, Notch signaling activates transcription of the mammalianhomolog of the Drosophila transcription factor hairy-enhancer of split(Hes). Transcriptional activation of Hes1 is mediated by de-repressionof CBF1/RBPJk upon binding by NICD in the nucleus. These facts have beenexploited to develop a reporter gene assay for Notch Signaling Hsieh, J.J., T. Henkel, P. Salmon, E. Robey, M. G. Peterson and S. D. Hayward(1996). “Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genesby a mechanism resembling that of Epstein-Barr virus EBNA2.” Mol CellBiol 16(3): 952-9; Lu, F. M. and S. E. Lux (1996). “Constitutivelyactive human Notchl binds to the transcription factor CBF1 andstimulates transcription through a promoter containing a CBF1-responsiveelement.” Proc Natl Acad Sci U S A 93(11): 5663-7).

Gamma secretase inhibitors have been observed to block NICD formation,and inhibit Notch signaling (De Strooper, B., W. Annaert, P. Cupers, P.Saftig, K. Craessaerts, J. S. Mumm, E. H. Schroeter, V. Schrijvers, M.S. Wolfe, W. J. Ray et al. (1999). “A presenilin-1-dependentgamma-secretase-like protease mediates release of Notch intracellulardomain.” Nature 398(6727): 518-22). Due to the importance of Notchsignaling in cell fate determination, and tissue differentiation duringboth development and in the adult, inhibition of Notch signaling bygamma secretase inhibitors is postulated to be a limiting factor intheir therapeutic utility. In order to identify selective gammasecretase inhibitors, we have employed a reporter gene based Notchsignaling assay using a constitutively active rat Notchl construct(ZEDN1) provided by Dr Gerry Weinmaster, who is at the University ofCalifornia at Los Angeles (UCLA) as described in Shawber, C., D.Nofziger, J. J. Hsieh, C. Lindsell, O. Bogler, D. Hayward and G.Weinmaster (1996). “Notch signaling inhibits muscle cell differentiationthrough a CBF1-independent pathway.” Development 122(12): 3765-73 incombination with the CBF1 repressible Luciferase reporter gene4xwtCBF1Luc (Hsieh, J. J., T. Henkel, P. Salmon, E. Robey, M. G.Peterson and S. D. Hayward (1996). “Truncated mammalian Notchl activatesCBF1/RBPJk-repressed genes by a mechanism resembling that ofEpstein-Barr virus EBNA2.” Mol Cell Biol 16(3): 952-9).

When 4xwtCBF1 Luciferase is co-transfected with NotchΔE (ZEDN1),γ-secretase cleavage of NotchΔE releases the Notch intracellular domain(NICD), which translocates to the nucleus and de-represses CBF1mediatedtranscriptional repression, leading to transcription of the Luciferasereporter gene. Luciferase activity is easily assayed in cell extractsusing commercially available kits. The activity of the reporter gene isdirectly correlated with gamma secretase cleavage of NotchΔE, and assuch, a reduction in Luciferase activity provides a convenient measureof inhibition of gamma secretase cleavage of NotchΔE. A comparison ofthe IC50 values of compounds for inhibition of Notch signaling versusinhibition of β-amyloid production in 293sw cells is employed to guidein the selection of compounds that have the desired property of potentinhibition of β-amyloid synthesis with minimal inhibition of NotchSignaling.

Compounds 84, 91, 139, 147, 237, 244, and 252, exhibit IC50 valueswithin the range of about 0.1 to 25 nM; compounds 2, 9, 22, 28, 80, 110,149, 151, 256, and 262, exhibit IC50 values within the range of about 25to 100 nM; an compounds 3, 5, 36, 49, 78, 115, 156, 264, 272, and 292,exhibit IC50 values within the range of about 100 to 1000 nM.

It will be apparent that the starting materials may be varied andadditional steps employed to produce the varied compounds encompassed bythe present invention. In some cases, protection of reactivefunctionalities may be necessary to achieve some of the abovetransformations. In general, such need for protecting groups, as well asthe conditions necessary to attach and remove such groups, will beapparent to those skilled in the art of organic synthesis.

The invention and the manner and process of making and using it, are nowdescribed in such full, clear, concise and exact terms as to enable anyperson skilled in the art to which it pertains, to make and use thesame. It is to be understood that the foregoing describes preferredembodiments of the invention and that modifications may be made thereinwithout departing from the spirit or scope of the invention as set forthin the claims. To particularly point out and distinctly claim thesubject matter regarded as invention, the following claims conclude thisspecification.

1. A compound of the formula:

or pharmaceutically acceptable salts thereof, wherein R₁ is C₂-C₆alkynyl, C₂-C₆ alkenyl, or C₁-C₈ alkyl wherein each is optionallysubstituted with 1, 2, or 3 groups that are independently C₁-C₆ alkoxy,OH, halogen, CN, C₁-C₆ thioalkoxy, phenyl, naphthyl, C₃-C₈ cycloalkyl,NH₂, NH(C₁-C₆) alkyl, N(C₁-C₆)alkyl (C₁-C₆ alkyl), —C(O) NH₂,—C(O)NH(C₁-C₆)alkyl, —C(O)N(C₁-C₆)alkyl(C₁-C₆)alkyl, —C(O)phenyl, orC₁-C₆ alkoxycarbonyl, wherein each of the cyclic groups is optionallysubstituted with 1, 2, 3, or 4 groups that are independently halogen,C₁-C₄ alkyl, C₁-C₄ alkoxy, NH₂, NH(C₁-C₆)alkyl, N(C₁-C₆)alkyl(C₁-C₆alkyl), —SO₂—(C₁-C₆)alkyl, or OH; or R₁ is C₃-C₈ cycloalkyl optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄hydroxyalkyl, or OH; or R₁ is heterocycloalkyl orheterocycloalkyl(C₁-C₄)alkyl wherein the heterocycloalkyl group ispiperidinyl, pyrrolidinyl, tetrahydrofuranyl, pyrazolyl, or morpholinyl,wherein the heterocycloalkyl groups are optionally substituted with 1 or2 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl,phenyl(C₁-C₄)alkyl, OH, halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or C₁-C₄alkoxycarbonyl; or R₁ is heteroaryl(C₁-C₄)alkyl, wherein the heteroarylgroup is pyridyl, pyrimidyl, furanyl, or thienyl and the heteroarylgroup is optionally substituted with 1, 2, or 3 groups that areindependently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkyl,C₁-C₄ alkoxy or OH; R₂ is C₁-C₈ alkyl, C₁-C₆ hydroxyalkyl, or C₂-C₈alkenyl, each of which is optionally substituted with 1, 2, or 3 groupsthat are independently 2H-chromenyl, 1,2,3,4-tetrahydronaphthalenyl,indolyl, 3,4-dihydronaphthalenyl, phenyl, naphthyl, C₃-C₈ cycloalkyl,benzofuranyl, indolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, pyridyl,pyrimidyl, C₁-C₄ alkyl, halogen, pyrazolyl, imidazolyl, oxazolyl,isoxazolyl, oxadiazolyl, thiazolyl, NO₂, thiadiazolyl, furanyl,triazolyl, or CN, wherein the cyclic portions of each of the above areoptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl,—C(O)N(C₁-C₆) alkyl (C₁-C₆) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, NO₂, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl; R₃ is H,halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkyl, or CN, R₄ is H,halogen, C₁-C₆ alkyl optionally substituted with —CO₂—(C₁-C₆ alkyl),C₁-C₆ alkoxy, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, CN, aryloxy,isocyanato, —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₆ alkanoyl, pyridyl,or phenyl; or R₃ and R₄ and the carbons to which they are attached forma heterocycloalkyl ring which is optionally substituted with 1, 2, or 3groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, orC₁-C₄ alkanoyl wherein the alkanoyl group is optionally substituted withup to 3 halogen atoms; R_(3′) is H, —SO₂—NR′R″, halogen, or R₄ andR_(3′) and the carbons to which they are attached form a phenyl ring; orR₄ and R_(3′) and the carbons to which they are attached form a1-oxa-2,3-diazacyclopentyl ring; R′ is H, C₁-C₆ alkyl,phenyl(C₁-C₄)alkyl, C₁-C₆ alkanoyl, phenyl(C₁-C₆)alkanoyl,pyridyl(C₁-C₄)alkyl, pyrimidyl(C₁-C₄)alkyl, pyridazyl(C₁-C₄)alkyl,pyrazinyl(C₁-C₄)alkyl, thienyl(C₁-C₄)alkyl, oxazolyl(C₁-C₄)alkyl,thiazolyl(C₁-C₄)alkyl, furanyl(C₁-C₄)alkyl, —SO₂-alkyl, —SO₂-phenyl,—SO₂-pyridyl, —SO₂-pyrimidyl, —SO₂-pyridazyl, —SO₂-pyrazinyl,—SO₂-thienyl, —SO₂-oxazolyl, —SO₂-thiazolyl, —SO₂-furanyl,pyridyl(C₁-C₆)alkanoyl, pyrimidyl(C₁-C₆)alkanoyl,pyridazyl(C₁-C₆)alkanoyl, pyrazinyl(C₁-C₆)alkanoyl,thienyl(C₁-C₆)alkanoyl, oxazolyl(C₁-C₆)alkanoyl,thiazolyl(C₁-C₆)alkanoyl, or furanyl(C₁-C₆)alkanoyl, wherein the alkylportion of the alkyl and alkanoyl groups are optionally substituted withhalogen or C₁-C₆ alkoxy, wherein the aryl, and heteroaryl groups areoptionally substituted with alkyl, alkoxy, halogen, haloalkyl,haloalkoxy, R″ is H, or C₁-C₆ alkyl, wherein the alkyl group isoptionally substituted with halogen.
 2. A compound according to claim 1,wherein R₁ is C₁-C₈ alkyl which is optionally substituted with 1, 2, or3 groups that are independently C₁-C₆ alkoxy, OH, halogen, CN, C₁-C₆thioalkoxy, phenyl, naphthyl, C₃-C₈ cycloalkyl, NH₂, NH(C₁-C₆)alkyl,N(C₁-C₆)alkyl(C₁-C₆ alkyl), —C(O)NH₂, —C(O)NH(C₁-C₆)alkyl,—C(O)N(C₁-C₆)alkyl(C₁-C₆)alkyl, —C(O)phenyl, or C₁-C₆ alkoxycarbonyl,wherein each of the cyclic groups is optionally substituted with 1, 2,3, or 4 groups that are independently halogen, C₁-C₄ alkyl, C₁-C₄alkoxy, NH₂, NH(C₁-C₆)alkyl, N(C₁-C₆)alkyl(C₁-C₆ alkyl),—SO₂—(C₁-C₆)alkyl, or OH.
 3. A compound according to claim 2, wherein R₃is H, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkyl, CN; R₄ is H,halogen, C₁-C₆ alkyl optionally substituted with —CO₂—(C₁-C₆ alkyl),C₁-C₆ alkoxy, C₁-C₄ haloalkyl, C₁-C₆ haloalkoxy, CN, aryloxy,isocyanato, —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₆ alkanoyl, oxazolyl,pyrazolyl, thiazolyl, pyridyl, furanyl or thienyl, phenyl; and R_(3′) isH, or halogen.
 4. A compound according to claim 3, wherein R₂ is C₁-C₈alkyl, or C₂-C₈ alkenyl, each of which is optionally substituted with 1,2, or 3 groups that are independently, 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,phenyl, naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl,1,4-benzodioxanyl, 1,3-benzodioxolyl, pyridyl, pyrimidyl, C₁-C₄ alkyl,halogen, —CO₂—(C₁-C₆ alkyl) , pyrazolyl, imidazolyl, oxazolyl,isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, or CN,wherein the cyclic portions of each of the above are optionallysubstituted with 1, 2, or 3 groups that are independently halogen, CO₂H,C₁-C₆ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl (C₁-C₆) alkyl, C₁-C₄ alkoxy optionally substituted with pyridyl,thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or 2; R₂₅ is C₁-C₆ alkyl,OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ and the nitrogen to which theyare attached represent pyrrolidinyl, piperidinyl, piperazinyl,morpholinyl, or imidazolidinyl.
 5. A compound according to claim 4,wherein R₁, is C₁-C₈ alkyl which is optionally substituted with OH.
 6. Acompound according to claim 5, wherein R₃ is H, halogen, C₁-C₆ alkyl,C₁-C₆ alkoxy, CF₃, CN; R₄ is H, halogen, C₁-C₆ alkoxy, C₁-C₆ alkyl, CF₃,OCF₃, CN, phenyloxy, —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″, C₁-C₄ alkanoyl,pyridyl, furanyl or thienyl, phenyl, or C₁-C₆ alkyl optionallysubstituted with —CO₂—(C₁-C₆ alkyl); R_(3′) is H, or halogen; R′ is H,C₁-C₆ alkyl, phenyl(C₁-C₄)alkyl, C₁-C₆ alkanoyl, phenyl(C₁-C₄)alkanoyl,pyridyl(C₁-C₄)alkyl, —SO₂-alkyl, —SO₂-phenyl, —SO₂-pyridyl,pyridyl(C₁-C₆)alkanoyl, wherein the alkyl portion of the alkyl andalkanoyl groups are optionally substituted with halogen or C₁-C₄ alkoxy,wherein the phenyl and pyridyl groups are optionally substituted withC₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, CF₃, OCF₃; R″ is H or C₁-C₆ alkyl,wherein the alkyl group is optionally substituted with halogen.
 7. Acompound according to claim 6, wherein R₂ is C₁-C₈ alkyl which isoptionally substituted with 1 or 2 phenyl groups, 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,phenyl, naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl,1,4-benzodioxanyl, 1,3-benzodioxolyl, pyridyl, pyrimidyl, triazolyl, orCN, wherein the cyclic portions of each of the above are optionallysubstituted with 1, 2, or 3 groups that are independently halogen, CO₂H,C₁-C₆ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆)alkyl (C₁-C₆) alkyl,C₁-C₄ alkoxy optionally substituted with pyridyl,thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or 2; R₂₅ is C₁-C₆ alkyl,OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ and the nitrogen to which theyare attached represent pyrrolidinyl, piperidinyl, piperazinyl,morpholinyl, or imidazolidinyl.
 8. A compound according to claim 7,wherein R₂ is C₁-C₈ alkyl which is optionally substituted with phenyl,benzofuranyl, 1,4-benzodioxanyl, or 1,3-benzodioxolyl, wherein thecyclic portions of each of the above are optionally substituted with 1,2, or 3 groups that are independently halogen, CO₂H, C₁-C₆alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl, —C(O)N(C₁-C₆) alkyl(C₁-C₆) alkyl, C₁-C₄ alkoxy optionally substituted with pyridyl,thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or 2; R₂₅ is C₁-C₆ alkyl,OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ and the nitrogen to which theyare attached represent pyrrolidinyl, piperidinyl, piperazinyl,morpholinyl, or imidazolidinyl.
 9. A compound according to claim 8,wherein R₂ is C₁-C₈ alkyl substituted with phenyl, wherein the phenyl isoptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, CO₂H, C₁-C₆ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl,—C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl.
 10. A compoundaccording to claim 9, wherein R₁ is C₁-C₈ hydroxyalkyl; R₃ is H,halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, CN; R₄ is H, halogen, C₁-C₄alkoxy, CF₃, OCF₃, CN, phenyloxy, —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″,C₁-C₄ alkanoyl, pyridyl, furanyl or thienyl, phenyl, or C₁-C₆ alkyloptionally substituted with —CO₂—(C₁-C₆ alkyl); R_(3′) is H, or halogen;R′ is H, C₁-C₄ alkyl, benzyl, C₁-C₆ alkanoyl, phenyl (C₁-C₄) alkanoyl,pyridyl(C₁-C₄)alkyl, —SO₂-alkyl, —SO₂-phenyl, —SO₂-pyridyl,pyridyl(C₁-C₆)alkanoyl, wherein the alkyl portion of the alkyl andalkanoyl groups are optionally substituted with halogen or C₁-C₄ alkoxy,wherein the phenyl and pyridyl groups are optionally substituted withC₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, CF₃, OCF₃; R″ is H or C₁-C₆ alkyl,wherein the alkyl group is optionally substituted with halogen.
 11. Acompound according to claim 10, wherein

R₁ is R₃ is H, halogen, methyl, methoxy, CF₃, or CN; R₄ is H, halogen,methyl, methoxy, CF₃, OCF₃, CN, —NHR′, or —NR′R″; R_(3′) is H, orhalogen; R′ is H, or C₁-C₄ alkyl; and R″ is H or C₁-C₆ alkyl, whereinthe alkyl group is optionally substituted with halogen.
 12. A compoundaccording to claim 5, wherein R₁ is C₁-C₈ alkyl; R₂ is C₁-C₈ alkylsubstituted with a phenyl group, benzofuranyl, 1,4-benzodioxanyl, or1,3-benzodioxolyl, wherein the phenyl group is optionally substitutedwith 1, 2, or 3 groups that are independently halogen, CO₂H, C₁-C₆alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₆) alkyl,—C(O)N(C₁-C₆)alkyl(C₁-C₆) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl; R₃ is H,halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CF₃, CN; R₄ is H, halogen, C₁-C₄alkoxy, CF₃, OCF₃, CN, phenyloxy, —SO₂—(C₁-C₆ alkyl), —NHR′, —NR′R″,C₁-C₄ alkanoyl, pyridyl, furanyl or thienyl, phenyl, or C₁-C₄ alkyloptionally substituted with —CO₂—(C₁-C₆ alkyl); R_(3′), is H, orhalogen; R′ is H, C₁-C₄ alkyl, benzyl, C₁-C₆ alkanoyl,phenyl(C₁-C₄)alkanoyl, pyridyl(C₁-C₄)alkyl, —SO₂-alkyl, —SO₂-phenyl,—SO₂-pyridyl, pyridyl(C₁-C₆)alkanoyl, wherein the alkyl portion of thealkyl and alkanoyl groups are optionally substituted with halogen orC₁-C₄ alkoxy, wherein the phenyl and pyridyl groups are optionallysubstituted with C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, CF₃, OCF₃; R″ is Hor C₁-C₆ alkyl, wherein the alkyl group is optionally substituted withhalogen.
 13. A compound according to claim 12, wherein R₁ is C₂-C₆alkyl; R₃ is H, halogen, methyl, methoxy, CF₃, or CN; R₄ is halogen,methyl, methoxy, CF₃, OCF₃, CN, —NHR′, or —NR′R″; R_(3′) is H, orhalogen; R′ is H, or C₁-C₄ alkyl; and R″ is H or C₁-C₆ alkyl, whereinthe alkyl group is optionally substituted with halogen.
 14. A compoundaccording to claim 6, wherein R₂ is C₃-C₈ alkenyl, optionallysubstituted with 1 or 2 groups that are independently phenyl, halogen,2H-chromenyl, 1,2,3,4-tetrahydronaphthalenyl, indolyl,3,4-dihydronaphthalenyl, naphthyl, C₃-C₈ cycloalkyl, benzofuranyl,indolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, pyridyl, C₁-C₄ alkyl,halogen, —CO₂—(C₁-C₄ alkyl), pyrazolyl, imidazolyl, oxazolyl,isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, orpyrimidyl; wherein the cyclic portions of each of the above areoptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl.
 15. A compoundaccording to claim 14, wherein R₂ is C₃-C₆ alkenyl, optionallysubstituted with 1 or 2 groups that are phenyl, halogen, pyrazolyl,imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl,or pyrimidyl; wherein the phenyl group is optionally substituted with 1,2, or 3 groups that are independently halogen, CO₂H, C₁-C₄alkoxycarbonyl, —C(O)NH₂, —C(O)NH(C₁-C₄) alkyl,—C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkoxy optionally substitutedwith pyridyl, thiazolyl, or methyl thiazol-5-yl, C₁-C₄ alkyl,—S(O)_(x)—R₂₅, —(C₁-C₄ alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or2; R₂₅ is C₁-C₆ alkyl, OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H,C₁-C₆ alkyl, phenyl(C₁-C₄ alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ andthe nitrogen to which they are attached represent pyrrolidinyl,piperidinyl, piperazinyl, morpholinyl, or imidazolidinyl.
 16. A compoundaccording to claim 1, wherein R₁ is C₃-C₈ cycloalkyl optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄hydroxyalkyl, or OH; or R₁ is heterocycloalkyl orheterocycloalkyl(C₁-C₄)alkyl wherein the heterocycloalkyl group ispiperidinyl, pyrrolidinyl, tetrahydrofuranyl, pyrazolyl, or morpholinyl,wherein the heterocycloalkyl groups are optionally substituted with 1 or2 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, phenyl,phenyl(C₁-C₄)alkyl, OH, halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, or C₁-C₄alkoxycarbonyl; or R₁ is heteroaryl(C₁-C₄)alkyl, wherein the heteroarylgroup is pyridyl, pyrimidyl, furanyl, or thienyl and the heteroarylgroup is optionally substituted with 1, 2, or 3 groups that areindependently halogen, CO₂H, C₁-C₄ alkoxycarbonyl, —C(O)NH₂,—C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄ alkyl,C₁-C₄ alkoxy or OH.
 17. A compound according to claim 16, wherein R₂ isC₁-C₈ alkyl, or C₂-C₈ alkenyl, each of which is optionally substitutedwith 1 or 2 groups that are independently, 2H-chromenyl,1,2,3,4-tetrahydronaphthalenyl, indolyl, 3,4-dihydronaphthalenyl,phenyl, naphthyl, C₃-C₈ cycloalkyl, benzofuranyl, indolyl,1,4-benzodioxanyl, 1,3-benzodioxolyl, pyridyl, pyrimidyl, C₁-C₄ alkyl,halogen, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl,thiazolyl, thiadiazolyl, furanyl, triazolyl, or CN, wherein the cyclicportions of each of the above are optionally substituted with 1, 2, or 3groups that are independently halogen, CO₂H, C₁-C₄ alkoxycarbonyl,—C(O)NH₂, —C(O)NH(C₁-C₄) alkyl, —C(O)N(C₁-C₄)alkyl(C₁-C₄) alkyl, C₁-C₄alkoxy, C₁-C₄ alkoxy optionally substituted with pyridyl, thiazolyl, ormethyl thiazol-5-yl, NO₂, C₁-C₄ alkyl, —S(O)_(x)—R₂₅, —(C₁-C₄alkyl)-S(O)_(x)—R₂₅, or OH; wherein x is 0, 1, or 2; R₂₅ is C₁-C₆ alkyl,OH, NR₂₆R₂₇; R₂₆ and R₂₇ are independently H, C₁-C₆ alkyl, phenyl(C₁-C₄alkyl), phenyl, or pyridyl; or R₂₆, R₂₇ and the nitrogen to which theyare attached represent pyrrolidinyl, piperidinyl, piperazinyl,morpholinyl, or imidazolidinyl.
 18. A pharmaceutical compositioncomprising a compound of claim 1 and at least one pharmaceuticallyacceptable carrier, solvent, adjuvant or excipient, or a combinationthereof.
 19. A method of treating a patient who has, or in preventing apatient from getting, a disease or condition selected from the groupconsisting of Alzheimer's disease, for helping prevent or delay theonset of Alzheimer's disease, for treating patients with mild cognitiveimpairment (MCI) and preventing or delaying the onset of Alzheimer'sdisease in those who would progress from MCI to AD, for treating Down'ssyndrome, for treating humans who have Hereditary Cerebral Hemorrhagewith Amyloidosis of the Dutch-Type, for treating cerebral amyloidangiopathy and preventing its potential consequences, i.e. single andrecurrent lobar hemorrhages, for treating other degenerative dementias,including dementias of mixed vascular and degenerative origin, dementiaassociated with Parkinson's disease, dementia associated withprogressive supranuclear palsy, dementia associated with cortical basaldegeneration, age related macular degeneration, or diffuse Lewy bodytype of Alzheimer's disease and who is in need of such treatment whichcomprises administration of a therapeutically effective amount of acompound of claim
 1. 20. A compound according to claim 1 that is(S)-4-chloro-N-cinnamyl-N-(1-hydroxy-4-methylpentan-2-yl)benzenesulfonamide;[(4-Chloro-benzenesulfonyl)-methyl-amino]-acetic acid ethyl ester;[2-(4-Chloro-benzenesulfonylimino)-imidazolidin-1-yl]-acetic acid;2-(4-Chloro-benzenesulfonylamino)-N-methyl-propionamide;2-[(4-Chloro-benzenesulfonyl)-(3,4-dimethoxy-benzyl)-amino]-3-phenyl-propionamide;2-[(4-Chloro-benzenesulfonyl)-(3-phenyl-propyl)-amino]-3-hydroxy-N-methyl-butyramide;3-[(4-Chloro-benzenesulfonyl)-(3,4-dimethoxy-benzyl)-amino]-piperidine-1-carboxylicacid tert-butyl ester;4-Chloro-N-(1,2-dimethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1,2-dimethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1,2,3,4-tetrahydro-naphthalen-2-yl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(2-pentyl-3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-butyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-(4-methoxy-benzyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-methyl-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-3-methyl-butyl)-N-propyl-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-pentyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-pentyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-chloro-N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;4-Chloro-N-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(2,3-dihydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2,3-dihydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2,4-dichloro-benzyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2,4-dichloro-benzyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2,4-difluoro-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-chloro-N-(2,4-difluorobenzyl)-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;4-Chloro-N-(2-cyano-ethyl)-N-cyclopropyl-benzenesulfonamide;4-Chloro-N-(2-cyano-ethyl)-N-cyclopropyl-benzenesulfonamide;4-Chloro-N-(2-cyano-ethyl)-N-ethyl-benzenesulfonamide;4-Chloro-N-(2-cyano-ethyl)-N-ethyl-benzenesulfonamide;4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;4-Chloro-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-benzenesulfonamide;4-Chloro-N-(2-hydroxy-cyclohexylmethyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(2-hydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2-hydroxy-propyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-methyl-propyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-methyl-propyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-propyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-naphthalen-1-yl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-naphthalen-1-yl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-4,5-dihydro-1-H-pyrazol-3-yl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-4,5-dihydro-1-H-pyrazol-3-yl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,3-dimethyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,3-dimethyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-hydroxy-1-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxy-2,2-dimethyl-propyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxymethyl-bicyclo[2.2.1]hept-2-yl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(4-methyl-cyclohexyl)-benzenesulfonamide;4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1R,2S)-2-hydroxy-1-(hydroxymethyl)-2-phenylethyl]benzenesulfonamide;4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S)-1-(hydroxymethyl)propyl]benzenesulfonamide;4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide;4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]benzenesulfonamide;4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S, 3R,4R)-3-(hydroxymethyl)bicyclo[2.2.1]hept-2-yl]benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1-(4-methanesulfonyl-phenyl)-ethyl]-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1-(4-methanesulfonyl-phenyl)-ethyl]-benzenesulfonamide;4-Chloro-N-(3-fluoro-4-methoxy-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-chloro-N-(3-fluoro-4-methoxybenzyl)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;4-Chloro-N-(3-hydroxy-butyl)-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-(4-chloro-6-fluoro-2H-chromen-3-ylmethyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(4-chloro-benzyl)-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-chloro-N-(4-chlorobenzyl)-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;4-Chloro-N-(4-diethylamino-1-methyl-butyl)-N-(3,4-dimethoxy-benzyl)-benzenesulfonamide;4-Chloro-N,N-dicyclohexyl-benzenesulfonamide;4-Chloro-N,N-diisopropyl-benzenesulfonamide;4-Chloro-N,N-divinyl-benzenesulfonamide;4-chloro-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]-N-(3-phenylpropyl)benzenesulfonamide;4-chloro-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]-N-(4-methoxybenzyl)benzenesulfonamide;4-chloro-N-[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N-methylbenzenesulfonamide;4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-[(2E)-2-methyl-3-phenylprop-2-en-1-yl]benzenesulfonamide;4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-[(2E)-3-phenylprop-2-en-1-yl]benzenesulfonamide;4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-{3-methoxy-4-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]benzyl}benzenesulfonamide;4-chloro-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N-methylbenzenesulfonamide;4-Chloro-N-[2-(3,4-dihydroxy-phenyl)-2-oxo-ethyl]-N-methyl-benzenesulfonamide;4-chloro-N-{[(1R,2S)-2-hydroxycyclohexyl]methyl}-N-{3-methoxy-4-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]benzyl}benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-butyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methylsulfanyl-propyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(4-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-pyridin-2-ylmethyl-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-prop-2-ynyl-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(tetrahydro-furan-2-ylmethyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methoxy-propyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(1-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-allyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-butyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methylsulfanyl-propyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(4-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-pyridin-2-ylmethyl-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-prop-2-ynyl-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(tetrahydro-furan-2-ylmethyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(3-methoxy-propyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(1-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-N-(2-methyl-allyl)-benzenesulfonamide;4-Chloro-N-cyanomethyl-N-methyl-benzenesulfonamide;4-Chloro-N-cyclohexyl-N-(2-hydroxy-ethyl)-benzenesulfonamide;4-Chloro-N-cyclohexyl-N-(2-hydroxy-ethyl)-benzenesulfonamide;4-Chloro-N-cyclohexyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-cyclohexyl-N-isopropyl-benzenesulfonamide;4-Chloro-N-cyclooctyl-N-(3,4-dimethoxy-benzyl)-benzenesulfonamide;4-Chloro-N-cyclopentyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-cyclopentyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-cyclopropylmethyl-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-cyclopropylmethyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-cyclopropylmethyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-ethyl-N-(2-pyridin-2-yl-ethyl)-benzenesulfonamide;4-Chloro-N-ethyl-N-[2-hydroxy-2-(3-hydroxy-phenyl)-ethyl]-benzenesulfonamide;4-Chloro-N-ethyl-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;4-Chloro-N-isopropyl-N-(2-pyridin-4-yl-ethyl)-benzenesulfonamide;4-Chloro-N-methyl-N-(1-methyl-piperidin-4-yl)-benzenesulfonamide;4-Chloro-N-methyl-N-(1-methyl-piperidin-4-yl)-benzenesulfonamide;4-Chloro-N-methyl-N-(2-pyridin-4-yl-ethyl)-benzenesulfonamide;4-Chloro-N-pyrrolidin-3-yl-benzenesulfonamide;N-(1,3-benzodioxol-5-ylmethyl)-4-chloro-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;N-(1-Benzyl-pyrrolidin-3-yl)-4-chloro-N-ethyl-benzenesulfonamide;N-(2-Amino-benzyl)-4-chloro-N-{3-methoxy-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-benzyl}-benzenesulfonamide;N-(2-Benzyl-cyclohexyl)-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;N-(4-Bromo-benzyl)-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;N-(4-bromobenzyl)-4-chloro-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide;N,N-Di-sec-butyl-4-chloro-benzenesulfonamide;N-[(1R)-1-benzyl-2-hydroxyethyl]-4-chloro-N-(3,4-dimethoxybenzyl)benzenesulfonamide;N-[(1S)-1-benzyl-2-hydroxyethyl]-4-chloro-N-(3,4-dimethoxybenzyl)benzenesulfonamide;N-[(4-chlorophenyl)sulfonyl]-N-(3,4-dimethoxybenzyl)-L-phenylalaninamide;N-[3-(4-tert-Butyl-phenyl)-2-methyl-propyl]-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;N2-[(4-chlorophenyl)sulfonyl]-N1-methyl-L-alaninamide;N-Allyl-4-chloro-N-cyclohexyl-benzenesulfonamide;N-Benzo[1,3]dioxol-5-ylmethyl-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;N-Benzofuran-2-ylmethyl-4-chloro-N-(1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;N-Benzofuran-2-ylmethyl-N-sec-butyl-4-chloro-benzenesulfonamide;N-Benzyl-4-chloro-N-(1-hydroxymethyl-propyl)-benzenesulfonamide;N-Benzyl-4-chloro-N-(2-hydroxy-cyclohexyl)-benzenesulfonamide;N-Benzyl-4-chloro-N-(2-hydroxymethyl-cyclohexyl)-benzenesulfonamide;N-benzyl-4-chloro-N-[(1R)-1-(hydroxymethyl)propyl]benzenesulfonamide;N-benzyl-4-chloro-N-[(1S,2R)-2-(hydroxymethyl)cyclohexyl]benzenesulfonamide;N-benzyl-4-chloro-N-[(1S, 2S)-2-hydroxycyclohexyl]benzenesulfonamide;N-Benzyl-N-sec-butyl-4-chloro-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(2-pentyl-3-phenyl-allyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(3,3-diphenyl-allyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(3-phenyl-allyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(3-phenyl-butyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(3-phenyl-propyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(4,6-dichloro-2H-chromen-3-ylmethyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-(4-chloro-6-fluoro-2H-chromen-3-ylmethyl)-benzenesulfonamide;N-sec-Butyl-4-chloro-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;N-tert-Butyl-2-(4-chloro-benzenesulfonylamino)-3-methyl-butyramide; orpharmaceutically acceptable salts thereof.
 21. A compound according toclaim 1 that is4-Chloro-N-cyclooctyl-N-(3,4-dimethoxy-benzyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,3-dimethyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(4-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1-hydroxymethyl-2-methyl-propyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxy-2,2-dimethyl-propyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-[1-(4-methanesulfonyl-phenyl)-ethyl]-benzenesulfonamide;3-[(4-Chloro-benzenesulfonyl)-(3,4-dimethoxy-benzyl)-amino]-piperidine-1-carboxylicacid tert-butyl ester;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(3-hydroxymethyl-bicyclo[2.2.1]hept-2-yl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(R-2-hydroxy-1-phenyl-ethyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(R-1-hydroxymethyl-2-phenyl-ethyl)-benzenesulfonamide;N-Benzyl-4-chloro-N-(1S, 2S-2-hydroxy-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-3-phenyl-allyl)-benzenesulfonamide;N-Benzo[1,3]dioxol-5-ylmethyl-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(3-fluoro-4-methoxy-benzyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(4-methoxy-benzyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(4-chloro-benzyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;N-(4-Bromo-benzyl)-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(2,4-difluoro-benzyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;R-N-sec-Butyl-4-chloro-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(R-1,2-dimethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-allyl)-benzenesulfonamide;3-[(4-Chloro-benzenesulfonyl)-(3-phenyl-allyl)-amino]-piperidine-1-carboxylicacid tert-butyl ester;4-[(4-Chloro-benzenesulfonyl)-(3-phenyl-allyl)-amino]-piperidine-1-carboxylicacid ethyl ester;R-N-sec-Butyl-4-chloro-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(R-1,2-dimethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-ethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-hydroxymethyl-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(2-hydroxy-propyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1,3-dimethyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(1-methyl-butyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(2-methoxy-1-methyl-ethyl)-N-(3-phenyl-propyl)-benzenesulfonamide;2S,3R-2-[(4-Chloro-benzenesulfonyl)-(3-phenyl-propyl)-amino]-3-hydroxy-N-methyl-butyramide;4-Chloro-N-(1S,2S-2-hydroxy-cyclopentyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-[(4-Chloro-benzenesulfonyl)-(3-phenyl-propyl)-amino]-piperidine-1-carboxylicacid ethyl ester;N-[3-(4-tert-Butyl-phenyl)-2-methyl-propyl]-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(4-chloro-6-fluoro-2H-chromen-3-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-pentyl-3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;N-Benzofuran-2-ylmethyl-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-butyl)-benzenesulfonamide;4-Chloro-N-cyclopropylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;R-N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;R-N-sec-Butyl-4-chloro-N-[3-(2-methoxy-phenyl)-allyl]-benzenesulfonamide;R-N-Benzofuran-2-ylmethyl-N-sec-butyl-4-chloro-benzenesulfonamide;R-N-sec-Butyl-4-chloro-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;R-N-sec-Butyl-4-chloro-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(3-fluoro-4-methoxy-benzyl)-benzenesulfonamide;4-Chloro-N-(2,4-difluoro-benzyl)-N-(2,5-dimethyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(4-methoxy-benzyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(2,5-dimethyl-cyclohexyl)-benzenesulfonamide;N-(4-Bromo-benzyl)-4-chloro-N-(2,5-dimethyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(2,5-dimethyl-cyclohexyl)-N-(2-methyl-3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(3,4-dimethoxy-benzyl)-N-(1R, 2S,5R-2-isopropyl-5-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-allyl)-benzenesulfonamide;N-(2-Benzyl-cyclohexyl)-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1,2,3,4-tetrahydro-naphthalen-2-yl)-benzenesulfonamide;4-Chloro-N-(4,6-dichloro-2H-chromen-3-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-1H-indol-2-ylmethyl)-benzenesulfonamide;4-Chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(1-methyl-3-phenyl-propyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-propyl-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-methyl-benzenesulfonamide;R-N-sec-Butyl-4-chloro-N-(1-chloro-3,4-dihydro-naphthalen-2-ylmethyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1,2-dimethyl-propyl)-benzenesulfonamide;4-Chloro-N-(S-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-[(4-Chloro-benzenesulfonyl)-(R-1-hydroxymethyl-3-methyl-butyl)-amino]-3-methyl-but-2-enoicacid ethyl ester;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-naphthalen-2-ylmethyl-benzenesulfonamide;4-Chloro-N-furan-2-ylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-furan-3-ylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(S-1-hydroxymethyl-3-methyl-butyl)-N-(3-phenyl-allyl)-benzenesulfonamide;4-Chloro-N-(S-1,2-dimethyl-propyl)-N-(3-phenyl-allyl)-benzenesulfonamide;N-(2-Bromo-3-phenyl-allyl)-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;N-But-2-enyl-4-chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-pentyl-benzenesulfonamide;4-Chloro-N-(3-furan-2-yl-2-methyl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(3-furan-2-yl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-pentyl)-benzenesulfonamide;4-Chloro-N-(2-ethyl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(2-ethyl-butyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-methyl-but-2-enyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-pyridin-3-yl-allyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-[3-(2-nitro-phenyl)-allyl]-benzenesulfonamide;4-[(4-Chloro-benzenesulfonyl)-(R-1-hydroxymethyl-3-methyl-butyl)-amino]-but-2-enoicacid ethyl ester;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(2-methyl-4-phenyl-pentyl)-benzenesulfonamide;4-Chloro-N-cyclohexylmethyl-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(2-chloro-3-phenyl-allyl)-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-[3-(3-chloro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-p-tolyl-allyl)-benzenesulfonamide;4-Chloro-N-[3-(4-dimethylamino-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-[3-(4-fluoro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-m-tolyl-allyl)-benzenesulfonamide;4-Chloro-N-[3-(3-fluoro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(R-1-hydroxymethyl-3-methyl-butyl)-N-(3-o-tolyl-allyl)-benzenesulfonamide;4-Chloro-N-[3-(4-chloro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-[3-(2-fluoro-phenyl)-allyl]-N-(R-1-hydroxymethyl-3-methyl-butyl)-benzenesulfonamide;4-Chloro-N-(6-methoxy-pyridin-3-ylmethyl)-N-(2-methyl-cyclohexyl)-benzenesulfonamide;4-Chloro-N-(6-chloro-pyridin-3-ylmethyl)-N-(2-methyl-cyclohexyl)-benzenesulfonamide;N-(6-Bromo-pyridin-3-ylmethyl)-4-chloro-N-(2-methyl-cyclohexyl)-benzenesulfonamide;and4-Chloro-N-(2-methyl-cyclohexyl)-N-(3-pyridin-3-yl-allyl)-benzenesulfonamide.